bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteinase 3 activity in sputum from subjects with alpha-1-antitrypsin deficiency and COPD
Authors: Sinden Nicola J. , Stockley Robert A. 
Published: August 2012

Chronic obstructive pulmonary disease (COPD) is associated with tissue damage believed to result from an imbalance between serine proteinases and their inhibitors. Although the role of neutrophil elastase (NE) has been studied, it is likely that other proteinases play a role. The importance of proteinase 3 (PR3) has not been established, as specific substrates have only recently been available.We studied clinically stable subjects with either alpha-1-antitrypsin (A1AT) deficiency or usual COPD with chronic bronchitis. Sol phase sputum was analysed for PR3 activity and concentration, NE activity and concentration, concentrations of airway inhibitors (A1AT, secretory leukoproteinase inhibitor and elafin) and markers of neutrophilic inflammation. 12 patients were also studied during exacerbations.PR3 activity was present in most sputum samples and greater than NE activity (which was largely undetectable) in both subject groups (A1AT deficiency median PR3 128 nM, interquartile range (IQR) 33–558 nM; NE 0 nM, IQR 0–0 nM; p=0.0043; COPD PR3 22 nM, IQR 0–103 nM; NE 0 nM, IQR 0–0 nM; p=0.015). PR3 activity was greater during exacerbations than in the stable state (p=0.037) and correlated with markers of neutrophilic inflammation.The regular identification of PR3 activity in sputum from stable subjects with A1AT deficiency or usual COPD suggests it may play a greater role in the pathophysiology than previously thought.
Riociguat for interstitial lung disease and pulmonary hypertension: a pilot trial
Authors: Hoeper Marius M. , Halank Michael , Wilkens Heinrike , Günther Andreas , Weimann Gerrit , Gebert Irmingard , Leuchte Hanno H. , Behr Jürgen 
Published: August 2012

We assessed the safety, tolerability and preliminary efficacy of riociguat, a soluble guanylate cyclase stimulator, in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD).In this open-label, uncontrolled pilot trial, patients received oral riociguat (1.0–2.5 mg three times daily) for 12 weeks (n=22), followed by an ongoing long-term extension (interim analysis at 12 months) in those eligible (n=15). Primary end-points were safety and tolerability. Secondary end-points included haemodynamic changes and 6-min walk distance (6MWD).Overall, 104 adverse events were reported, of which 25 were serious; eight of the latter were considered drug-related. After 12 weeks of therapy, mean cardiac output increased (4.4±1.5 L·min−1to 5.5±1.8 L·min−1), pulmonary vascular resistance (PVR) decreased (648±207 dyn·s−1·cm−5to 528±181 dyn·s−1·cm−5) and mean pulmonary artery pressure (mPAP) remained unchanged compared with baseline. Arterial oxygen saturation decreased but mixed-venous oxygen saturation slightly increased. The 6MWD increased from 325±96 m at baseline to 351±111 m after 12 weeks.Riociguat was well tolerated by most patients and improved cardiac output and PVR, but not mPAP. Further studies are necessary to evaluate the safety and efficacy of riociguat in patients with PH-ILD.
On the generalized Hyers-Ulam-Rassias stability problem of radical functional equations
Authors: Kim Seong Sik , Cho Yeol Je , Eshaghi Gordji Madjid 
Published: August 2012

Abstract
In this paper, the generalized Hyers-Ulam-Rassias stability problem of radical quadratic and radical quartic functional equations in quasi-β-Banach spaces and then the stability by using subadditive and subquadratic functions for radical functional equations in

(
β
,
p
)

-Banach spaces are given.

MSC:39B82, 39B52, 46H25.
Responses to pandemic ASO3-adjuvanted A/California/07/09 H1N1 influenza vaccine in human immunodeficiency virus-infected individuals
Authors: Kelly Deborah , Burt Kimberley , Missaghi Bayan , Barrett Lisa , Keynan Yoav , Fowke Keith , Grant Michael 
Published: August 2012

Abstract

Background
Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied.

Objective
Assess vaccine-related effects on CD4+ T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic.

Methods
A single dose of ArepanrixTM split vaccine including 3.75 μg A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1–5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4+ T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals.

Results
Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4+ T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4+ T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4+ T cell numbers, which was greater amongst responders.

Conclusions
We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals without pre-existing antibodies against H1N1 HA and a minor transient fall in CD4+ T cell numbers, which was accentuated in responders. A single injection of the ArepanrixTM pandemic A/California/07/2009 H1N1 HA split vaccine may be insufficient to induce protective immunity in HIV-infected individuals without pre-existing anti-H1N1 HA responses.
Production of engineered long-life and male sterile Pelargonium plants
Authors: García-Sogo Begoña , Pineda Benito , Roque Edelín , Antón Teresa , Atarés Alejandro , Borja Marisé , Beltrán José Pío , Moreno Vicente , Cañas Luis Antonio 
Published: August 2012

Abstract

Background
Pelargonium is one of the most popular garden plants in the world. Moreover, it has a considerable economic importance in the ornamental plant market. Conventional cross-breeding strategies have generated a range of cultivars with excellent traits. However, gene transfer via Agrobacterium tumefaciens could be a helpful tool to further improve Pelargonium by enabling the introduction of new genes/traits. We report a simple and reliable protocol for the genetic transformation of Pelargonium spp. and the production of engineered long-life and male sterile Pelargonium zonale plants, using the pSAG12::ipt and PsEND1::barnase chimaeric genes respectively.

Results
The pSAG12::ipt transgenic plants showed delayed leaf senescence, increased branching and reduced internodal length, as compared to control plants. Leaves and flowers of the pSAG12::ipt plants were reduced in size and displayed a more intense coloration. In the transgenic lines carrying the PsEND1::barnase construct no pollen grains were observed in the modified anther structures, which developed instead of normal anthers. The locules of sterile anthers collapsed 3–4 days prior to floral anthesis and, in most cases, the undeveloped anther tissues underwent necrosis.

Conclusion
The chimaeric construct pSAG12::ipt can be useful in Pelargonium spp. to delay the senescence process and to modify plant architecture. In addition, the use of engineered male sterile plants would be especially useful to produce environmentally friendly transgenic plants carrying new traits by preventing gene flow between the genetically modified ornamentals and related plant species. These characteristics could be of interest, from a commercial point of view, both for pelargonium producers and consumers.
Predictor of poor coronary collaterals in chronic kidney disease population with significant coronary artery disease
Authors: Hsu Po-Chao , Juo Suh-Hang , Su Ho-Ming , Chen Szu-Chia , Tsai Wei-chung , Lai Wen-Ter , Sheu Sheng-Hsiung , Lin Tsung-Hsien 
Published: August 2012

Abstract

Background
Coronary collateral circulation plays an important role to protect myocardium from ischemia, preserve myocardial contractility and reduce cardiovascular events. Chronic kidney disease (CKD) is associated with poor coronary collateral development and cardiovascular outcome. However, limited research investigates the predictors for collateral development in the CKD population.

Methods
We evaluated 970 consecutive patients undergoing coronary angiography and 202 patients with CKD, defined as a glomerular filtration rate less than 60 ml/min/1.73 m2, were finally analyzed. The collateral scoring system developed by Rentrop was used to classify patients into poor (grades 0 and 1) or good (grades 2 and 3) collateral group.

Results
The patients with poor collateral (n = 122) had a higher incidence of hypertension (82% vs 63.8%, p = 0.005), fewer diseased vessels numbers (2.1 ± 0.9 vs 2.6 ± 0.6, p < 0.001) and a trend to be diabetic (56.6% vs. 43.8%, p = 0.085) or female sex (37.7% vs. 25.0%, p = 0.067). Multivariate analysis showed hypertension (odd ratio (OR) 2.672, p = 0.006), diabetes (OR 1.956, p = 0.039) and diseased vessels numbers (OR 0.402, p < 0.001) were significant predictors of poor coronary collaterals development. Furthermore, hypertension and diabetes have a negative synergistic effect on collateral development (p = 0.004 for interaction).

Conclusions
In the CKD population hypertension and diabetes might negatively influence the coronary collaterals development.
Role of aldo-keto reductases and other doxorubicin pharmacokinetic genes in doxorubicin resistance, DNA binding, and subcellular localization
Authors: Heibein Allan D , Guo Baoqing , Sprowl Jason A , MacLean David A , Parissenti Amadeo M 
Published: August 2012

Abstract

Background
Since proteins involved in chemotherapy drug pharmacokinetics and pharmacodynamics have a strong impact on the uptake, metabolism, and efflux of such drugs, they likely play critical roles in resistance to chemotherapy drugs in cancer patients.

Methods
To investigate this hypothesis, we conducted a whole genome microarray study to identify difference in the expression of genes between isogenic doxorubicin-sensitive and doxorubicin-resistant MCF-7 breast tumour cells. We then assessed the degree of over-representation of doxorubicin pharmacokinetic and pharmacodynamic genes in the dataset of doxorubicin resistance genes.

Results
Of 27,958 Entrez genes on the array, 7.4 per cent or 2,063 genes were differentially expressed by ≥ 2-fold between wildtype and doxorubicin-resistant cells. The false discovery rate was set at 0.01 and the minimum p value for significance for any gene within the “hit list” was 0.01. Seventeen and 43 per cent of doxorubicin pharmacokinetic genes were over-represented in the hit list, depending upon whether the gene name was identical or within the same gene family, respectively. The most over-represented genes were within the 1C and 1B families of aldo-keto reductases (AKRs), which convert doxorubicin to doxorubicinol. Other genes convert doxorubicin to other metabolites or affect the influx, efflux, or cytotoxicity of the drug. In further support of the role of AKRs in doxorubicin resistance, we observed that, in comparison to doxorubicin, doxorubincol exhibited dramatically reduced cytotoxicity, reduced DNA-binding activity, and strong localization to extra nuclear lysosomes. Pharmacologic inhibition of the above AKRs in doxorubicin-resistant cells increased cellular doxorubicin levels, restored doxorubicin cytotoxicity and re-established doxorubicin localization to the nucleus. The properties of doxorubicinol were unaffected.

Conclusions
These findings demonstrate the utility of using curated pharmacokinetic and pharmacodynamic knowledge bases to identify highly relevant genes associated with doxorubicin resistance. The induction of one or more of these genes was found to be correlated with changes in the drug’s properties, while inhibiting one specific class of these genes (the AKRs) increased cellular doxorubicin content and restored drug DNA binding, cytotoxicity, and subcellular localization.
Somatic symptoms beyond those generally associated with a whiplash injury are increased in self-reported chronic whiplash. A population-based cross sectional study: the Hordaland Health Study (HUSK)
Authors: Myrtveit Solbjørg Makalani , Skogen Jens Christoffer , Wenzel Hanne Gro , Mykletun Arnstein 
Published: August 2012

Abstract

Background
Chronic whiplash leads to considerable patient suffering and substantial societal costs. There are two competing hypothesis on the etiology of chronic whiplash. The traditional organic hypothesis considers chronic whiplash and related symptoms a result of a specific injury. In opposition is the hypothesis that chronic whiplash is a functional somatic syndrome, and related symptoms a result of society-induced expectations and amplification of symptoms.
According to both hypotheses, patients reporting chronic whiplash are expected to have more neck pain, headache and symptoms of anxiety and depression than the general population. Increased prevalence of somatic symptoms beyond those directly related to a whiplash neck injury is less investigated.
The aim of this study was to test an implication derived from the functional hypothesis: Is the prevalence of somatic symptoms as seen in somatization disorder, beyond symptoms related to a whiplash neck injury, increased in individuals self-reporting chronic whiplash? We further aimed to explore recall bias by comparing the symptom profile displayed by individuals self-reporting chronic whiplash to that among those self-reporting a non-functional injury: fractures of the hand or wrist. We explored symptom load, etiologic origin could not be investigated in this study.

Methods
Data from the Norwegian population-based “Hordaland Health Study” (HUSK, 1997–99); N = 13,986 was employed. Chronic whiplash was self-reported by 403 individuals and fractures by 1,746. Somatization tendency was measured using a list of 17 somatic symptoms arising from different body parts and organ systems, derived from the research criteria for somatization disorder (ICD-10, F45).

Results
Chronic whiplash was associated with an increased level of all 17 somatic symptoms investigated (p<0.05). The association was moderately strong (group difference of 0.60 standard deviation), only partly accounted for by confounding. For self-reported fractures symptoms were only slightly elevated. Recent whiplash was more commonly reported than whiplash-injury a long time ago, and the association of interest weakly increased with time since whiplash (r = 0.016, p = 0.032).

Conclusions
The increased prevalence of somatic symptoms beyond symptoms expected according to the organic injury model for chronic whiplash, challenges the standard injury model for whiplash, and is indicative evidence of chronic whiplash being a functional somatic syndrome.
Association of smoking status, cumulative smoking, duration of smoking cessation, age of starting smoking, and depression in Korean adults
Authors: Yun Woo-Jun , Shin Min-Ho , Kweon Sun-Seog , Ryu So-Yeon , Rhee Jung-Ae 
Published: August 2012

Abstract

Background
Many previous studies did not sufficiently control for several confounding factors that may affect the association between smoking and depression, such as socioeconomic status. We investigated the association between depression and smoking status, smoking exposure, duration of smoking cessation, and age of starting smoking while controlling for socioeconomic factors.

Methods
This study was based on a community health survey performed in Jeollanam-do, South Korea, between September and November 2009. In total, 20,084 subjects (9,118 males and 10,966 females) were included in the analysis. Information on smoking characteristics, such as smoking status, pack-years of smoking, and age of starting smoking, was collected using a standardized questionnaire. Depression was defined using the Korean CES-D score.

Results
The odds ratios (ORs) of depression were 1.35 (0.92–1.98) for former smokers and 1.77 (1.27–2.48) for current-smokers among males, and 2.67 (1.38–5.16) for former smokers and 3.72 (2.11–6.54) for current-smokers among females, after adjusting for other confounding factors. Compared to light smoking, heavy smoking was significantly associated with depression in males [OR = 3.97, 95% confidence interval (CI) = 1.42–11.14], but not in females (OR = 1.24, 95% CI = 0.73–2.09). No significant associations between depression and age of starting smoking and duration of smoking cessation were observed among former smokers.

Conclusions
Our data demonstrate that smoking is strongly associated with depression, particularly among females. These findings suggest that depression prevention may need to be combined with smoking prevention and that different strategies may be needed for males and females.
Laparoscopic and open postchemotherapy retroperitoneal lymph node dissection in patients with advanced testicular cancer – a single center analysis
Authors: Busch Jonas , Magheli Ahmed , Erber Barbara , Friedersdorff Frank , Hoffmann Ivan , Kempkensteffen Carsten , Weikert Steffen , Miller Kurt , Schrader Mark , Hinz Stefan 
Published: August 2012

Abstract

Background
The open approach represents the gold standard for postchemotherapy retroperitoneal lymph node dissection (O-PCLND) in patients with residual testicular cancer. We analyzed laparoscopic postchemotherapy retroperitoneal lymph node dissection (L-PCLND) and O-PCLND at our institution.

Methods
Patients underwent either L-PCLND (n = 43) or O-PCLND (n = 24). Categorical and continuous variables were compared using the Fisher exact test and Mann–Whitney U test respectively. Overall survival was evaluated with the log-rank test.

Results
Primary histology was embryonal cell carcinomas (18 patients), pure seminoma (2 cases) and mixed NSGCTs (47 patients). According to the IGCCCG patients were categorized into “good”, “intermediate” and “poor prognosis” disease in 55.2%, 14.9% and 20.8%, respectively. Median operative time for L-PCLND was 212 min and 232 min for O-PCLND (p = 0.256). Median postoperative duration of drainage and hospital stay was shorter after L-PCLND (0.0 vs. 3.5 days; p < 0.001 and 6.0 vs. 11.5 days; p = 0.002). Intraoperative complications occurred in 21.7% (L-PCLND) and 38.0% (O-PCLND) of cases with 19.5% and 28.5% of Clavien Grade III complications for L-PCLND and O-PCLND, respectively (p = 0.224). Significant blood loss (>500 ml) was almost equally distributed (8.6% vs. 14.2%: p = 0.076). No significant differences were observed for injuries of major vessels and postoperative complications (p = 0.758; p = 0.370). Tumor recurrence occurred in 8.6% following L-PCLND and in 14.2% following O-PCLND with a mean disease-free survival of 76.6 and 89.2 months, respectively. Overall survival was 83.3 and 95.0 months for L-PCNLD and O-PCLND, respectively (p = 0.447).

Conclusions
L-PCLND represents a safe surgical option for well selected patients at an experienced center.
Effects of salivary protein flow and indigenous microorganisms on initial colonization of Candida albicans in an in vivo model
Authors: Kanaguchi Norihiko , Narisawa Naoki , Ito Tatsuro , Kinoshita Yosuke , Kusumoto Yasuka , Shinozuka Osamu , Senpuku Hidenobu 
Published: August 2012

Abstract

Background

Candida albican s is a dimorphic fungus that is part of the commensal microbial flora of the oral cavity. When the host immune defenses are impaired or when the normal microbial flora is disturbed, C. albicans triggers recurrent infections of the oral mucosa and tongue. Recently, we produced NOD/SCID.e2f1
-/- mice that show hyposalivation, decrease of salivary protein flow, lack IgA and IgG in saliva, and have decreased NK cells. Our objective was to characterize C. albicans infection and biofilm formation in mice.

Methods
NOD/SCID.e2f1
-/- mice were used as an animal model for C. albicans infection. C. albicans yeast and hyphal forms solutions were introduced in the oral cavity after disinfection by Chlorhexidine.

Results
The numbers of C. albicans colonized and decreased in a time-dependent manner in NOD/SCID.e2f1
+/+ after inoculation. However, the colonization levels were higher in NOD/SCID.e2f1
+/+ than NOD/SCID.e2f1
-/- mice. In the mice fed 1% sucrose water before inoculation, C. albicans sample was highly contaminated by indigenous microorganisms in the oral cavity; and was not in the mice fed no sucrose water. The colonization of C. albicans was not influenced by the contamination of indigenous microorganisms. The hyphal form of C. albicans restricted the restoration of indigenous microorganisms. The decreased saliva in NOD/SCID.e2f1
-/- did not increase the colonization of C. albicans in comparison to NOD/SCID.e2f1
+/+ mice. We suggest that the receptor in saliva to C. albicans may not be sufficiently provided in the oral cavity of NOD/SCID.e2f1
-/- mice.

Conclusion
The saliva protein flow may be very important for C. albicans initial colonization, where the indigenous microorganisms do not affect colonization in the oral cavity.
Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction - an experimental study
Authors: Fu Mingqiang , Zhou Jingmin , Qian Juying , Jin Xuejuan , Zhu Hongmin , Zhong Chunlin , Fu Michael , Zou Yunzeng , Ge Junbo 
Published: August 2012

Abstract

Background
Adiponectin is reported to relate with cardiovascular diseases, we sought to examine whether adiponectin is associated with disease progression of heart failure from hypertension in rats in comparison with other known biomarkers and echocardiographic parameters. Spontaneously hypertensive rats (SHR, n = 35), aged 1 month, were used and followed up to 18 months. High frequency echocardiography was performed both at baseline and every 3 months thereafter. Moreover, serum levels of N-terminal pro-natriuretic peptide (NT-proBNP) and interleukin-6 (IL-6) as well as serum level and tissue expression of adiponectin were determined at the same time as echocardiography.

Results
The results clearly demonstrated time-dependent progression of hypertension and heart dysfunction as evidenced by gradually increased left ventricular mass index, NT-proBNP, IL-6 as well as gradually decreased cardiac function as assessed by echocardiography. Meanwhile, tissue and serum adiponectin decreased from 3 months and reached plateau until 12 months in parallel with decreasing of cardiac diastolic function. Thereafter, adiponectin levels increased prior to occurrence of systolic dysfunction. Adiponectin concentration is inversely related with NT-proBNP, IL-6 and E/E′ (correlation coefficient (r) = −0.756 for NT-proBNP, p < 0.001, -0.635 for IL-6, p = 0.002, and −0.626 for E/E′, p = 0.002, respectively) while positively correlated with E/A and E′/A′ (r = 0.683 for E/A, p = 0.001, 0.671 for E′/A′, p = 0.001, respectively). No difference for adiponectin distribution among visceral adipose tissues was found.

Conclusion
Adiponectin through its biphasic serum level is a useful biomarker during transition from diastolic dysfunction to systolic dysfunction.