bluuebunny/crossref_metadata_2025 huggingface dataset:
Benefit of repetitive intrathecal triamcinolone acetonide therapy in predominantly spinal multiple sclerosis: prediction by upper spinal cord atrophy
Authors: Lukas Carsten , Bellenberg Barbara , Hahn Horst K. , Rexilius Jan , Drescher Robert , Hellwig Kerstin , Köster Odo , Schimrigk Sebastian
Published: September 2009

Intrathecal injection of triamcinolone acetonide (TCA) has been shown to provide substantial benefit in a subset of progressive multiple sclerosis (MS) patients with predominant spinal symptoms. We examined whether atrophy of the upper spinal cord (USC) as measured by MRI can serve as a predictive marker for response to repetitive intrathecal TCA application. Repetitive administration of 40 mg TCA was performed in 31 chronic progressive MS patients up to six times within 3 weeks. Expanded Disability Status Scale (EDSS) and maximum walking distance (WD) were assessed before and after the treatment cycle. Cervical 3D T1-weighted images were acquired on a 1.5T scanner at baseline. Mean cross-sectional area of the USC was determined using a semi-automated volumetry method. Results were compared with a group of 29 healthy controls to group patients into those with and without atrophy. Results show a negative correlation between the degree of USC atrophy and treatment benefit. A higher treatment benefit in patients with little USC atrophy but short initial maximum WD was observed. Absence of USC atrophy as measured on MRI is a predictive marker for intrathecal TCA therapy outcome in progressive MS. Patients with initial poor walking abilities, but only little or no atrophy, benefited most from TCA therapy.
Instrumentation-Specific Infection After Anterior Cruciate Ligament Reconstruction
Authors: Parada Stephen A. , Grassbaugh Jason A. , DeVine John G. , Arrington Edward D.
Published: September 2009

Background:

Anterior cruciate ligament (ACL) reconstruction is uncommonly complicated by postoperative infections, the causes of which are rarely identified.

Hypothesis/Purpose:

The goal of this study was to characterize the relationship between methodological sterilization failure and ACL reconstruction infection at an army medical center.

Study Design:

Case series.

Methods:

Demographic, clinical, and laboratory data were collected on 5 postoperative infections during a 14-week period in 2003. All ACL reconstructions completed within the past 6 years at the institution were reviewed to establish a baseline infection rate.

Results:

There was a 14-week period in which 5 cases of infection occurred postoperatively, an infection rate of 12.2%. Previous and subsequent to the identified period, the established rate of infection after ACL reconstruction was 0.3%. There were no violations of sterile technique noted in any of the identified cases. All cases utilized hamstring autograft. All cases also used the DePuy Mitek Intrafix system for tibial fixation of the graft. Two of these cases had positive cultures.

Conclusions:

An isolated series of increased infection rate led to an investigation into the sterile technique. This revealed gross biomaterial remaining inside instrumentation common to all the cases, the DePuy Mitek Intrafix system. The modular cannulated hex driver, made to fit over a small caliber wire, had no wire brushes of a small-enough diameter for the cleaning and sterilization procedure. After recognition of infection, all patients were treated with surgical irrigation and debridement of the affected knee, as well as individualized antibiotic therapy. Patients were followed postoperatively and no patients required revision ACL reconstruction or radical debridement of the graft.
Selectin-mediated activation of endothelial cells induces expression of CCL5 and promotes metastasis through recruitment of monocytes
Authors: Läubli Heinz , Spanaus Katharina-Susanne , Borsig Lubor
Published: September 2009

Hematogenous metastasis is promoted by interactions of tumor cells with leukocytes, platelets, and the endothelium in the local intravascular microenvironment. Here we show that the activation of the microvascular endothelium results in recruitment of monocytes to metastatic tumor cells and promotes the establishment of the metastatic microenvironment. This inflammatory-like endothelial response was observed in microvascular endothelial cells only. Microarray analysis of microvascular endothelial cells cocultured with tumor cells in the presence of leukocytes and platelets revealed a specific gene expression profile. Selectin-mediated interactions of tumor cells with platelets and leukocytes activated endothelial cells and induced production of C-C chemokine ligand 5 (CCL5). Inhibition of CCL5-dependent monocyte recruitment during the early phase of metastasis by a CCL5 receptor antagonist strongly reduced tumor cell survival and attenuated metastasis. Collectively, these findings demonstrate that the endothelial expression of CCL5 contributes to the formation of a permissive metastatic microenvironment.
Dasatinib treatment of chronic-phase chronic myeloid leukemia: analysis of responses according to preexisting BCR-ABL mutations
Authors: Müller Martin C. , Cortes Jorge E. , Kim Dong-Wook , Druker Brian J. , Erben Philipp , Pasquini Ricardo , Branford Susan , Hughes Timothy P. , Radich Jerald P. , Ploughman Lynn , Mukhopadhyay Jaydip , Hochhaus Andreas
Published: September 2009

Dasatinib is a BCR-ABL inhibitor with 325-fold higher potency than imatinib against unmutated BCR-ABL in vitro. Imatinib failure is commonly caused by BCR-ABL mutations. Here, dasatinib efficacy was analyzed in patients recruited to phase 2/3 trials with chronic-phase chronic myeloid leukemia with or without BCR-ABL mutations after prior imatinib. Among 1043 patients, 39% had a preexisting BCR-ABL mutation, including 48% of 805 patients with imatinib resistance or suboptimal response. Sixty-threedifferent BCR-ABL mutations affecting 49 amino acids were detected at baseline, with G250, M351, M244, and F359 most frequently affected. After 2 years of follow-up, dasatinib treatment of imatinib-resistant patients with or without a mutation resulted in notable response rates (complete cytogenetic response: 43% vs 47%) and durable progression-free survival (70% vs 80%). High response rates were achieved with different mutations except T315I, including highly imatinib-resistant mutations in the P-loop region. Impaired responses were observed with some mutations with a dasatinib median inhibitory concentration (IC50) greater than 3nM; among patients with mutations with lower or unknown IC50, efficacy was comparable with those with no mutation. Overall, dasatinib has durable efficacy in patients with or without BCR-ABL mutations. All trials were registered at http://www.clinicaltrials.gov as NCT00123474, NCT00101660, and NCT00103844.
Differential gene expression and cytokine production from neutrophils in asthma phenotypes
Authors: Baines K. J. , Simpson J. L. , Bowden N. A. , Scott R. J. , Gibson P. G.
Published: September 2009

Asthma is characterised into eosinophilic and non-eosinophilic phenotypes based on inflammatory cell patterns in airway secretions. Neutrophils are important in innate immunity, and are increased in the airways in non-eosinophilic asthma. The present study investigated the activity of neutrophils in asthma phenotypes.

Participants with eosinophilic (n = 8) and non-eosinophilic asthma (n = 9) and healthy controls (n = 11) underwent sputum induction and blood collection. Neutrophils were isolated and cultured with or without lipopolysaccharide. Cytokines were measured by ELISA, and gene expression was analysed using a gene expression microarray and quantitative PCR.

In non-eosinophilic asthma, blood neutrophils released significantly higher levels of interleukin-8 at rest. Cytokine gene expression and sputum neutrophil protein production did not differ between asthma subtypes. Microarrays demonstrated closely related expression profiles from participants with non-eosinophilic asthma that were significantly distinct from those in eosinophilic asthma. A total of 317 genes were significantly altered in resting neutrophils from participants with non-eosinophilic asthmaversuseosinophilic asthma, including genes related to cell motility and regulation of apoptosis.

Non-eosinophilic and eosinophilic asthma are associated with specific gene expression profiles, providing further evidence that these phenotypes of asthma involve different molecular mechanisms of disease pathogenesis at the systemic level. The mechanisms of non-eosinophilic asthma may involve enhancement of blood neutrophil chemotaxis and survival.
Health-related quality of life and unmet needs in patients with primary ciliary dyskinesia
Authors: Pifferi M. , Bush A. , Di Cicco M. , Pradal U. , Ragazzo V. , Macchia P. , Boner A. L.
Published: September 2009

Few studies have evaluated the quality of life of patients with primary ciliary dyskinesia (PCD). We sought to determine the health impact of the disease as well as the unmet needs in a large group of patients.

Questionnaires were either posted or e-mailed to known patients with PCD and published online. Questionnaires included the St George's Respiratory Questionnaire, the Medical Outcomes Study Short Form-36 and a questionnaire that we produced to obtain information on age of diagnosis, symptoms and likely PCD-specific problems of these patients.

78 subjects (96% of those invited) answered all the questionnaires. Patients were diagnosed at a mean age of 9.4 yrs. Progressive worsening of the disease was observed and adherence to physiotherapy was found to be poor, particularly in adolescents and adults. Patients with the highest treatment burden had a worse quality of life. Over time patients become progressively less interested in treating their disease and adherence to treatment modalities decreases.

PCD is associated with a progressive and continuous impact on the physical and mental health of the patients. Earlier identification of the patients and better strategies aimed at improving compliance with care are urgently needed.
Novel strategy to identify genetic risk factors for COPD severity: a genetic isolate
Authors: van Diemen C. C. , Postma D. S. , Aulchenko Y. S. , Snijders P. J. L. M. , Oostra B. A. , van Duijn C. M. , Boezen H. M.
Published: September 2009

Studies using genetic isolates with limited genetic variation may be useful in chronic obstructive pulmonary disease (COPD) genetics, but are thus far lacking. The associations between single nucleotide polymorphisms (SNPs) in candidate genes and lung function in COPD were studied in a genetic isolate.

In 91 subjects with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage ≥1 COPD, who were members of an extended pedigree including 6,175 people from the Genetic Research in Isolated Populations study, 32 SNPs were analysed in 13 candidate genes: a disintegrin and metalloprotease domain 33 gene (ADAM33), transforming growth factor-β1 gene (TGFB1), matrix metalloprotease-1 gene (MMP1),MMP2,MMP9,MMP12, tissue inhibitor of metalloprotease-1 gene (TIMP1), surfactant protein A1 gene (SFTPA1),SFTPA2,SFTPB,SFTPD, glutathione S-transferase P1 gene (GSTP1), and haem oxygenase 1 gene (HMOX1). Their relation to forced expiratory volume in 1 s (FEV1), inspiratory vital capacity (IVC) and FEV1/IVC were studied using restricted maximum likelihood linear mixed modelling, accounting for pedigree structure. Significant associations were replicated in the general Vlagtwedde/Vlaardingen study.

Six SNPs inTGFB1,SFTPA1,SFTPA2andSFTPDwere significantly associated with FEV1/IVC in subjects with GOLD stage ≥1 COPD. Two SNPs inTGFB1(C to T substitution at nucleotide -509 and substitution of leucine 10 with proline (Leu10Pro)), Leu50Val inSFTPA1and Ala160Thr inSFTPDshowed evidence suggestive of association with FEV1/IVC in subjects with GOLD stage ≥2 COPD. TheTGFB1associations were replicated in GOLD stage ≥2 patients from the Vlagtwedde/Vlaardingen population, with similar effect sizes.

It was shown that a genetic isolate can be used to determine the genetics of lung function, which can be replicated in COPD patients from an independent population.
The effect of surgery on lung volume and conventional monitoring parameters in ventilated newborn infants
Authors: Proquitté H. , Freiberger O. , Yilmaz S. , Bamberg C. , Degenhardt P. , Roehr C. C. , Wauer R. R. , Schmalisch G.
Published: September 2009

In newborn infants, thoraco-abdominal surgery is a serious intervention with respect to gas exchange and lung mechanics. This prospective clinical study compared surgery-induced changes in functional residual capacity (FRC) and ventilation inhomogeneity (VI) indices with changes in conventional monitoring parameters.

Of 29 ventilated newborns (mean weight 2,770±864 g at surgery), 13, nine and seven underwent thoracic, abdominal or congenital diaphragmatic hernia (CDH) surgery, respectively. The multiple breath washout (MBWO) technique using heptafluoropropane as tracer gas (Babylog® 8000; Dräger, Lübeck, Germany) was performed <6 h before surgery, 22–24 h after surgery and <6 h before extubation. Gas exchange, respiratory mechanics, FRC and VI index data were recorded.

Thoraco-abdominal surgery resulted in changes to FRC and VI indices in a procedure-specific manner; however, these changes were not reflected in conventional mechanical or ventilatory monitoring parameters. FRC decreased in non-CDH infants, while FRC increased and VI indices decreased in CDH infants. Despite improvements, the differences in FRC and VI between CDH and non-CDH infants indicated persistent impaired lung function in CHD infants.

MBWO can be advantageously used to measure the effect of surgery on the lung. While FRC and VI indices changed following surgery, conventional monitoring parameters did not.
Nasopharyngoscopic evaluation of oral appliance therapy for obstructive sleep apnoea
Authors: Chan A. S. L. , Lee R. W. W. , Srinivasan V. K. , Darendeliler M. A. , Grunstein R. R. , Cistulli P. A.
Published: September 2009

This study aimed to explore the effect of mandibular advancement splints (MAS) on upper airway anatomy during wakefulness in obstructive sleep apnoea (OSA).

Patients commencing treatment for OSA with MAS were recruited. Response to treatment was defined by a ≥50% reduction in the apnoea/hypopnoea index. Nasopharyngoscopy was performed in the supine position.

Nasopharyngoscopy was performed in 18 responders and 17 nonresponders. Mandibular advancement caused an increase in the calibre of the velopharynx (mean±sem+40±10%), with relatively minor changes occurring in the oropharynx and hypopharynx. An increase in cross-sectional area of the velopharynx with mandibular advancement occurred to a greater extent in responders than nonresponders (+56±16%versus+22±13%; p<0.05). Upper airway collapse during the Müller manoeuvre, relative to the baseline cross-sectional area, was greater in nonresponders than responders in the velopharynx (-94±4%versus-69±9%; p<0.01) and oropharynx (-37±6%versus-16±3%; p<0.01). When the Müller manoeuvre was performed with mandibular advancement, airway collapse was greater in nonresponders than responders in the velopharynx (-80±11%versus+9±37%; p<0.001), oropharynx (-36±6%versus-20±5%; p<0.05) and hypopharynx (-64±6%versus-42±6%; p<0.05).

These results indicate that velopharyngeal calibre is modified by MAS treatment and this may be useful for predicting treatment response.
Phosphoinositide 3-kinase γ required for lipopolysaccharide-induced transepithelial neutrophil trafficking in the lung
Authors: Reutershan J. , Saprito M. S. , Wu D. , Rückle T. , Ley K.
Published: September 2009

Phosphoinositide 3-kinase γ(PI3Kγ) is a critical mediator of directional cell movement. Here, we sought to characterise the role ofPI3Kγin mediating the different steps of polymorphonuclear leukocyte (PMN) trafficking in the lung.

In a murine model of lipopolysaccharide (LPS)-induced lung injury, PMN migration into the different lung compartments was determined inPI3Kγgene-deficient (PI3Kγ-/-) and wild-type mice. Bone marrow chimeras were created to characterise the role ofPI3Kγon haematopoieticversusnonhaematopoietic cells. A small-moleculePI3Kγinhibitor was testedin vitroandin vivo.

PMN adhesion to the pulmonary endothelium and transendothelial migration into the lung interstitium was enhanced inPI3Kγ-/-mice. However, transepithelial migration into the alveolar space was reduced in these mice. When irradiatedPI3Kγ-/-mice were reconstituted with bone marrow from wild-type mice, migratory activity into the alveolar space was restored partially. A small-moleculePI3Kγinhibitor reduced chemokine-induced PMN migrationin vitrowhen PMNs or epithelial cells, but not when endothelial cells, were treated. The inhibitor also reduced LPS-induced PMN migrationin vivo.

We conclude thatPI3Kγis required for transepithelial but not for transendothelial migration in LPS-induced lung injury. Inhibition ofPI3Kγactivity may be effective at curbing excessive PMN infiltration in lung injury.
Calculating gambling odds and lung ages for smokers
Authors: Hansen J. E. , Sun X-G. , Wasserman K.
Published: September 2009

Interpreting spirometry as normal or abnormal using 95% confidence limits can obscure milder airflow decreases. Other analyses might better persuade cigarette smokers to quit.

High-quality spirometric data of ambulatory never- and current-smokers of African-, European- and Latin-American ethnicity from the Third National Health and Nutrition Evaluation Survey (n>9000) were analysed. We desired to calculate, for each decade of life, the odds that specific ratios of forced expiratory volume in 1 s to 6 s (%FEV1/FEV6) and to forced vital capacity (%FEV1/FVC) values came from a current- or never-smoker. We also desired to develop new, simpler and better formulas to estimate changes in physiological lung age (Δlung age) for males and females.

For each decade of life, odds increase strikingly that smoking decreases %FEV1/FEV6and %FEV1/FVC. At least for these three ethnicities, Δlung age can be easily calculated as the product of (predicted - actual) %FEV1/FEV6× 4 or (predicted - actual) %FEV1/FVC × 3. Through the sixth decade of life, smokers' Δlung age increase rapidly but little thereafter, presumably due to the inabilities of older smokers to participate in the survey or their deaths.

Using odds and Δlung ages rather than traditional 95% confidence limits might better persuade smokers to quit.
Pulmonary changes induced bytrans,trans-2,4-decadienal, a component of cooking oil fumes
Authors: Wang C-K. , Chang L. W. , Chang H. , Yang C-H. , Tsai M-H. , Tsai H-T. , Lin P.
Published: September 2009

Cooking oil fumes (COF) are known to be associated with respiratory diseases and risk of lung cancer. Involvement oftrans,trans-2,4-decadienal (tt-DDE), a major component in COF, is suspected.

Male CD-1® (ICR) mice were intratracheally instilled with either 8 or 24 mg·kg−1tt-DDE weekly for 8 weeks. Total numbers and types of cells in bronchoalveolar lavage fluid (BALF), as well as pathological changes, and inflammatory gene modulations in the lung tissues were assessed.

We demonstrated that the number of alveolar macrophages in the BALF was significantly increased intt-DDE-exposed animals. Histologically, there was a dose-correlated increase in epithelial hyperplasia and granulomatous nodules at the bronchioloalveolar junctions (BAJ). Although both Clara and alveolar type II cells were present in the BAJ lesion, only Clara cells were actively proliferative. However, only alveolar type II cells were found in the BAJ granulomatous nodules. Enhanced accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a known pro-carcinogenic factor, was also detected in many alveolar type II cells at the BAJ lesions.

As both BAJ hyperplasia and enhanced pSTAT3 accumulation are known risk factors associated with increased lung adenocarcinoma development, these findings suggest thattt-DDE may pose a risk in lung carcinogenesis.
Gene promoter methylation assayed in exhaled breath, with differences in smokers and lung cancer patients
Authors: Han Weiguo , Wang Tao , Reilly Andrew A , Keller Steven M , Spivack Simon D
Published: September 2009

Background

There is a need for new, noninvasive risk assessment tools for use in lung cancer population screening and prevention programs.

Methods

To investigate the technical feasibility of determining DNA methylation in exhaled breath condensate, we applied our previously-developed method for tag-adapted bisulfite genomic DNA sequencing (tBGS) for mapping of DNA methylation, and adapted it to exhaled breath condensate (EBC) from lung cancer cases and non-cancer controls. Promoter methylation patterns were analyzed in DAPK, RASSF1A and PAX5β promoters in EBC samples from 54 individuals, comprised of 37 controls [current- (n = 19), former- (n = 10), and never-smokers (n = 8)] and 17 lung cancer cases [current- (n = 5), former- (n = 11), and never-smokers (n = 1)].

Results

We found: (1) Wide inter-individual variability in methylation density and spatial distribution for DAPK, PAX5β and RASSF1A. (2) Methylation patterns from paired exhaled breath condensate and mouth rinse specimens were completely divergent. (3) For smoking status, the methylation density of RASSF1A was statistically different (p = 0.0285); pair-wise comparisons showed that the former smokers had higher methylation density versus never smokers and current smokers (p = 0.019 and p = 0.031). For DAPK and PAX5β, there was no such significant smoking-related difference. Underlying lung disease did not impact on methylation density for this geneset. (4) In case-control comparisons, CpG at -63 of DAPK promoter and +52 of PAX5β promoter were significantly associated with lung cancer status (p = 0.0042 and 0.0093, respectively). After adjusting for multiple testing, both loci were of borderline significance (padj = 0.054 and 0.031). (5) The DAPK gene had a regional methylation pattern with two blocks (1)~-215~-113 and (2) -84 ~+26); while similar in block 1, there was a significant case-control difference in methylation density in block 2 (p = 0.045); (6)Tumor stage and histology did not impact on the methylation density among the cases. (7) The results of qMSP applied to EBC correlated with the corresponding tBGS sequencing map loci.

Conclusion

Our results show that DNA methylation in exhaled breath condensate is detectable and is likely of lung origin. Suggestive correlations with smoking and lung cancer case-control status depend on individual gene and CpG site examined.
Actomyosin contractility controls cell surface area of oligodendrocytes
Authors: Kippert Angelika , Fitzner Dirk , Helenius Jonne , Simons Mikael
Published: September 2009

Background

To form myelin oligodendrocytes expand and wrap their plasma membrane multiple times around an axon. How is this expansion controlled?

Results

Here we show that cell surface area depends on actomyosin contractility and is regulated by physical properties of the supporting matrix. Moreover, we find that chondroitin sulfate proteoglycans (CSPG), molecules associated with non-permissive growth properties within the central nervous system (CNS), block cell surface spreading. Most importantly, the inhibitory effects of CSPG on plasma membrane extension were completely prevented by treatment with inhibitors of actomyosin contractility and by RNAi mediated knockdown of myosin II. In addition, we found that reductions of plasma membrane area were accompanied by changes in the rate of fluid-phase endocytosis.

Conclusion

In summary, our results establish a novel connection between endocytosis, cell surface extension and actomyosin contractility. These findings open up new possibilities of how to promote the morphological differentiation of oligodendrocytes in a non-permissive growth environment.

See related minireview by Bauer and ffrench-Constant: http://www.jbiol.com/content/8/8/78
The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma
Authors: He Di , Xu Qin , Yan Ming , Zhang Ping , Zhou Xiaojian , Zhang Zhiyuan , Duan Wenhu , Zhong Laiping , Ye Dongxia , Chen Wantao
Published: September 2009

Background

Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated.

Methods

Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA.

Results

The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased.

Conclusion

The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The NF-kappa B signaling pathway plays an important role in this process. Therefore, combining GA and celastrol may be a promising modality for treating oral squamous cell carcinoma.
Changes in health-related quality of life and clinical implications in Chinese patients with chronic cough
Authors: Ma Wei , Yu Li , Wang Yu , Li Xin , LÜ Hanjing , Qiu Zhongmin
Published: September 2009

Background

Chronic cough has negative effects on quality of life. However, the changes in health-related quality of life and clinical implications remain unclear in Chinese patients with chronic cough.

Methods

A standard Chinese version of Leicester cough questionnaire (LCQ) was developed by an established translation procedure and its repeatability was assessed in a preliminary study involving 20 untreated patients with stable chronic cough. The quality of life was measured with the Short form-36 health survey and compared between 110 patients with chronic cough and 90 healthy volunteers. The changes in health-related quality of life were evaluated in the patients with chronic cough with the LCQ just before the specific treatment was initiated and a week after the cough had resolved completely. Cough threshold with inhaled capsaicin, expressed as the lowest concentration of capsaicin required for the induction of ≥5 coughs, was also measured.

Results

The repeatability of the Chinese version of the LCQ was validated at a four day interval with the intraclass correlation coefficients of 0.89-0.94 for total and domain score (n = 20). The scores of the Short form-36 health survey were significantly lower in patients with chronic cough than those in healthy volunteers. In general, there was no significant difference in overall quality of life between different causes of chronic cough or genders although embarrassment, frustration and sleep disturbance were more common in female patients, as indicated by the LCQ. However, the successful treatment of cough obviously increased the total scores of the LCQ from 14.2 ± 2.7 to 19.5 ± 1.9 (t = 13.7, P < 0.0001). There was a significant correlation between the total score of the LCQ and physical (r = 0.39, P < 0.0001) or mental (r = 0.30, P < 0.001) component summary of the Short form-36 health survey but not between the LCQ and capsaicin cough threshold.

Conclusion

The quality of life is significantly impaired in Chinese patients with chronic cough. The Chinese version of the LCQ is a valid measure of cough related quality of life and is repeatable and responsive.
Arterial tortuosity syndrome in two Italian paediatric patients
Authors: Ritelli Marco , Drera Bruno , Vicchio Mariano , Puppini Giovanni , Biban Paolo , Pilati Mara , Prioli Maria Antonia , Barlati Sergio , Colombi Marina
Published: September 2009

Background

Arterial tortuosity syndrome (ATS) (OMIM #208050) is a rare autosomal recessive connective tissue disorder characterized by tortuosity and elongation of the large and medium-sized arteries, propensity to aneurysms formation, vascular dissection, and pulmonary arteries stenosis. ATS is caused by mutations in SLC2A10 gene, encoding for the facilitative glucose transporter 10 (GLUT10). So far, 17 SLC2A10 mutations have been reported in 32 families, two of which were Italian with a total of five patients. Here we present the clinical and molecular characterization of two novel Italian paediatric ATS patients.

Methods

The exons and intronic flanking regions of SLC2A10 gene were amplified and direct sequencing was performed.

Results

In both patients, the involvement of major- and medium-sized arteries was characteristic; the nonvascular connective tissue manifestations were mild and not pathognomic of the disorder. Both patients, born from non-consanguineous parents, were heterozygous for two different SLC2A10 mutations, three of which were recurrent and one was novel (p.Arg231Trp). This mutation is localized at the endofacial loop between the transmembrane domains 6 and 7 of GLUT10.

Conclusion

Two novel ATS patients were characterized at clinical and molecular level. Overall, four ATS unrelated families are known in Italy so far. Though ATS clinical delineation improved in the last years, further works in the comprehension of disease presentation and complications onset, particularly in paediatric age, and on ATS molecular basis are needed to add new insights for diagnosis and prevention strategies for related complications.
Selective Estrogen Receptor Modulators Decrease Reactive Astrogliosis in the Injured Brain: Effects of Aging and Prolonged Depletion of Ovarian Hormones
Authors: Barreto George , Santos-Galindo María , Diz-Chaves Yolanda , Pernía Olga , Carrero Paloma , Azcoitia Iñigo , Garcia-Segura Luis M.
Published: September 2009

After brain injury, astrocytes acquire a reactive phenotype characterized by a series of morphological and molecular modifications, including the expression of the cytoskeletal protein vimentin. Previous studies have shown that estradiol down-regulates reactive astrogliosis. In this study we assessed whether raloxifene and tamoxifen, two selective estrogen receptor modulators, have effects similar to estradiol in astrocytes. We also assessed whether aging and the timing of estrogenic therapy after ovariectomy influence the action of the estrogenic compounds. Four groups of animals were studied: 1) young rats, ovariectomized at 2 months of age; 2) middle-aged rats, ovariectomized at 8 months of age; 3) aged rats, ovariectomized at 18 months of age; and 4) aged rats, ovariectomized at 2 months and sham operated at 18 months of age. Fifteen days after ovariectomy or sham surgery, animals received a stab wound brain injury and the treatment with the estrogenic compounds. The number of vimentin-immunoreactive astrocytes after injury was significantly higher in the hippocampus of aged rats after a long-term ovariectomy compared with aged animals after a short-term ovariectomy and middle-aged rats. In addition, reactive astrocytes were more numerous in the two groups of aged animals than in young animals. Despite these differences, the estrogenic compounds reduced reactive astrogliosis in all animal groups. These findings indicate that estradiol, raloxifene, and tamoxifen are potential candidates for the control of astrogliosis in young and older individuals and after a prolonged depletion of ovarian hormones.
Colony-Stimulating Factor 2 (CSF-2) Improves Development and Posttransfer Survival of Bovine Embryos Produced in Vitro
Authors: Loureiro Bárbara , Bonilla Luciano , Block Jeremy , Fear Justin M. , Bonilla Aline Q. S. , Hansen Peter J.
Published: September 2009

In this study, we tested the role of colony-stimulating factor 2 (CSF2) as one of the regulatory molecules that mediate maternal effects on embryonic development during the preimplantation period. Our objective was to verify effects of CSF2 on blastocyst yield, determine posttransfer survival, and evaluate properties of the blastocyst formed after CSF2 treatment. In vitro, CSF2 increased the percentage of oocytes that became morulae and blastocysts. Blastocysts that were treated with CSF2 tended to have a greater number of inner cell mass cells and had a higher ratio of inner cell mass to trophectoderm cells. There was no effect of CSF2 on the incidence of apoptosis. Treatment with CSF2 from d 5 to 7 after insemination increased embryonic survival as indicated by improved pregnancy rate at d 30–35 of gestation. Moreover, treatment with CSF2 from either d 1–7 or 5–7 after insemination reduced pregnancy loss after d 30–35. Results indicate that treatment with CSF2 can affect embryonic development and enhance embryo competence for posttransfer survival. The fact that treatment with CSF2 during such a narrow window of development altered embryonic function much later in pregnancy suggests that CSF2 may exert epigenetic effects on the developing embryo that result in persistent changes in function during the embryonic and fetal periods of development.
Evidence for a Homodimeric Structure of Human Monocarboxylate Transporter 8
Authors: Visser W. Edward , Philp Nancy J. , van Dijk Thamar B. , Klootwijk Wim , Friesema Edith C. H. , Jansen Jurgen , Beesley Philip W. , Ianculescu Alexandra G. , Visser Theo J.
Published: September 2009

The human monocarboxylate transporter 8 (hMCT8) protein mediates transport of thyroid hormone across the plasma membrane. Association of hMCT8 mutations with severe psychomotor retardation and disturbed thyroid hormone levels has established its physiological relevance, but little is still known about the basic properties of hMCT8. In this study we present evidence that hMCT8 does not form heterodimers with the ancillary proteins basigin, embigin, or neuroplastin, unlike other MCTs. In contrast, it is suggested that MCT8 exists as monomer and homodimer in transiently and stably transfected cells. Apparently hMCT8 forms stable dimers because the complex is resistant to denaturing conditions and dithiothreitol. Cotransfection of wild-type hMCT8 with a mutant lacking amino acids 267–360 resulted in formation of homo-and heterodimers of the variants, indicating that transmembrane domains 4–6 are not involved in the dimerization process. Furthermore, we explored the structural and functional role of the 10 Cys residues in hMCT8. All possible Cys>Ala mutants did not behave differently from wild-type hMCT8 in protein expression, cross-linking experiments with HgCl2 and transport function. Our findings indicate that individual Cys residues are not important for the function of hMCT8 or suggest that hMCT8 has other yet-undiscovered functions in which cysteines play an essential role.
A Novel Isoform of Human LZIP Negatively Regulates the Transactivation of the Glucocorticoid Receptor
Authors: Kang Hyereen , Kim Yoon Suk , Ko Jesang
Published: September 2009

The human leucine zipper protein (LZIP) is a basic leucine zipper transcription factor that is involved in leukocyte migration, tumor suppression, and endoplasmic reticulum stress-associated protein degradation. Although evidence suggests a diversity of roles for LZIP, its function is not fully understood, and the subcellular localization of LZIP is still controversial. We identified a novel isoform of LZIP and characterized its function in ligand-induced transactivation of the glucocorticoid receptor (GR) in COS-7 and HeLa cells. A novel isoform of human LZIP designated as “sLZIP” contains a deleted putative transmembrane domain (amino acids 229–245) of LZIP and consists of 345 amino acids. LZIP and sLZIP were ubiquitously expressed in a variety of cell lines and tissues, with LZIP being much more common. sLZIP was mainly localized in the nucleus, whereas LZIP was located in the cytoplasm. Unlike LZIP, sLZIP was not involved in the chemokine-mediated signal pathway. sLZIP recruited histone deacetylases (HDACs) to the promoter region of the mouse mammary tumor virus luciferase reporter gene and enhanced the activities of HDACs, resulting in suppression of expression of the GR target genes. Our findings suggest that sLZIP functions as a negative regulator in glucocorticoid-induced transcriptional activation of GR by recruitment and activation of HDACs.
Sonic hedgehog-dependent synthesis of laminin α1 controls basement membrane assembly in the myotome
Authors: Anderson Claire , Thorsteinsdóttir Sólveig , Borycki Anne-Gaëlle
Published: September 2009

Basement membranes have essential structural and signalling roles in tissue morphogenesis during embryonic development, but the mechanisms that control their formation are still poorly understood. Laminins are key components of basement membranes and are thought to be essential for initiation of basement membrane assembly. Here, we report that muscle progenitor cells populating the myotome migrate aberrantly in the ventral somite in the absence of sonic hedgehog (Shh) signalling, and we show that this defect is due to the failure to form a myotomal basement membrane. We reveal that expression of Lama1, which encodes laminin α1, a subunit of laminin-111, is not activated in Shh-/- embryos. Recovery of Lama1 expression or addition of exogenous laminin-111 to Shh-/-;Gli3-/- embryos restores the myotomal basement membrane, demonstrating that laminin-111 is necessary and sufficient to initiate assembly of the myotomal basement membrane. This study uncovers an essential role for Shh signalling in the control of laminin-111 synthesis and in the initiation of basement membrane assembly in the myotome. Furthermore, our data indicate that laminin-111 function cannot be compensated by laminin-511.
Necl2 regulates epidermal adhesion and wound repair
Authors: Giangreco Adam , Jensen Kim B. , Takai Yoshimi , Miyoshi Jun , Watt Fiona M.
Published: September 2009

Differential expression of cell adhesion molecules regulates stem cell location, self-renewal and lineage selection under steady state conditions and during tissue repair. We show that the intercellular adhesion protein nectin-like molecule 2 (Necl2) is highly expressed in bulge stem cells of adult human and mouse hair follicles. Overexpression of Necl2 in cultured human keratinocytes led to upregulation of calcium/calmodulin-associated Ser/Thr kinase (CASK), increased calcium-independent intercellular adhesion,and inhibition of cell motility and in vitro wound healing. Although the rate of cell proliferation was reduced, terminal differentiation was unaffected. To assess the role of Necl2 in vivo, we examined the epidermis of Necl2-null mice and developed transgenic mice that expressed Necl2 in the basal layer of murine epidermis. Necl2 overexpression led to a reduction in S-phase cells and an increase in quiescent cells retaining DNA label in the bulge. Although epidermal homeostasis appeared normal in both transgenic and knockout mice, wound healing was markedly delayed. Necl2 overexpression resulted in reduced proliferation and increased levels of CASK and E-cadherin at the leading edge of healing wounds, consistent with its effects in culture. Our results demonstrate that Necl2 is involved in regulating epidermal stem cell quiescence and location.
Mucocutaneous manifestations in 150 HIV-infected Indian patients and their relationship with CD4 lymphocyte counts
Authors: Sud N , Shanker V , Sharma A , Sharma N L , Gupta M
Published: September 2009

Mucocutaneous findings in 150 HIV+ve cases (F, 79; M, 71) were evaluated over a one-year period. Mucocutaneous manifestations were seen in 96% with 2.9 mean number of dermatoses and mean cluster of differentiation (CD4) count of 196.33 cells/mm3. The highest number of mean dermatoses, 3.29, was seen in individuals with severe immunosuppression. The most common mucocutaneous manifestation seen was candidiasis (35.33%), followed by seborrhoeic dermatitis (31.33%), oral pigmentation (29.33%), xerosis/ichthyosis (22.67%), pyodermas (22%), periodontitis (17.33%) and nail pigmentation (16.67%). Patient stratification according to the WHO immunological staging, according to CD4 counts, showed a statistically significant association ( P < 0.05) for candidiasis, scabies, paronychia, oral pigmentation and diffuse hair loss. Nail and oral pigmentary changes, trichomegaly and subcutaneous fungal infections caused by dermatophytes were highlights of the study. Incidences of xerosis/ichthyosis, pyodermas, scabies and molluscum contagiosum reported in our study were higher and pruritic popular eruptions was lower than those in previous Indian studies. Cutaneous neoplasms were not seen in the present study.
Perspective—The Interdependence of Private and Public Interests
Authors: Mahoney Joseph T. , McGahan Anita M. , Pitelis Christos N.
Published: September 2009

The predominant focus in research on organizations is on private or public institutions without consistent consideration of their interdependencies. The emphasis in scholarship on private or public interests has strengthened as disciplinary and professional knowledge has deepened: Management scholars, for example, tend to consider the corporation as the unit of analysis, whereas scholars of public policy often analyze governmental, multilateral, community, and nonprofit organizations. This article advocates a partial merging of these research agendas on the grounds that private and public interests cannot be fully understood if they are conceived independently. We review three major areas of activity today in which public and private interests interact in complex ways and maintain that current theories of organization science can be deployed to understand these interactions better. We also suggest that theories of public-private interaction require development and describe a concept called global sustainable value creation, which may be used to identify organizational and institutional configurations and strategies conducive to worldwide, intertemporal efficiency and value creation. We conclude that scholarship on organizations would advance if private-public interactions were evaluated by the criterion of global sustainable value creation, and we identify organizational research opportunities that jointly consider public and private interests.
Selected Human Factors Issues in Information Visualization
Authors: Robertson George , Czerwinski Mary , Fisher Danyel , Lee Bongshin
Published: September 2009

Information visualization is the art and science of representing abstract information in a visual form that enables human users to gain insight through their perceptual and cognitive capabilities. In this chapter, we examine some key human factors aspects of information visualizations. We begin with an overview of major information visualization principles and techniques, with background on human factors issues that drove the development of those principles and techniques. Next, we look at how human capabilities are best used by visualization, focusing on the use of animation in visualizations. Then we look at the emerging area of large display visualization, examining how visualization changes when a user cannot easily see the entire visualization in detail. We then discuss evaluation of information visualizations, discussing aspects of utility and usability. We conclude by discussing remaining challenges in information visualization and how the field is changing today.
Augmented Cognition: An Overview
Authors: Stanney Kay M. , Schmorrow Dylan D. , Johnston Matthew , Fuchs Sven , Jones David , Hale Kelly S. , Ahmad Ali , Young Peter
Published: September 2009

Augmented cognition is a form of human-systems interaction in which a tight coupling between user and computer is achieved via physiological and neurophysiological sensing of a user's cognitive state. This interactive paradigm seeks to revolutionize the manner in which humans engage with computers by leveraging this knowledge of cognitive state to precisely adapt user-system interaction in real time. This review provides an overview of contemporary works in the field of augmented cognition and details regarding the three main components of an augmented cognition system: cognitive state sensors, adaptation strategies, and control systems. The review provides a perspective on the field as well as insights into the many challenges that lie ahead for those who endeavor to realize the full potential of augmented cognition.
A History and Primer of Human Performance Modeling
Authors: Byrne Michael D. , Pew Richard W.
Published: September 2009

Human performance models are abstractions, usually mathematical or computational, that attempt to explain or predict human behavior in a particular domain or task. This includes a wide range of techniques and approaches, from ideas that are most likely familiar to the majority of human factors professionals (such as signal detection theory) to more novel and complex approaches (such as computational models of dual tasking while driving). This chapter provides a sampling of modeling approaches and domains to which those approaches have been applied; for a more in-depth review, see Pew and Mavor (1998). We also discuss some of the issues faced by modelers as well as describe some of the rich history of the modeling endeavor over the past 50 years.
Determination of Physical, Acoustical, Mechanical, and Chemical Properties of Fresh Young Coconut Fruit for Maturity Separation
Authors: Terdwongworakul Anupun , Jarimopas Bundit , Chaiyapong Songtham , Singh Sher Paul , Singh Jay
Published: September 2009

Young coconut is a popular tropical fruit featuring soft white aromatic flesh and sweet white or transparent juice. As most coconut pickers are relatively unskilled, the harvested crop tends to be distinguished by the collection of fruit of varying levels of maturity. This research has sought to improve the accuracy of grading-packaging systems by developing correlations between maturity levels and the physical, acoustical, mechanical, and chemical properties of the fruit. Results show that maturity significantly affects the specific gravity, shell rupture force, shell secant modulus, flesh penetrating force, flesh firmness, total soluble solids, titratable acidity, flesh thickness (FT), and natural frequency of young coconut at p<0.05. The FT expressed the highest linear correlation with maturity among the properties observed. Fruit orientation, sound impact point, and maturity significantly affected the natural frequency of young coconut at p<0.05. Impacting the ridge of a young coconut gave significantly different natural frequency with maturity regardless of the impact position. The optimum impact point was observed to be midway between the fruit equator and the stem on the ridge. Applying the defined physical and chemical properties to the discriminant model, the maturity of young coconut could be classified with an accuracy of 94.0 %. Analysis employing partial least squares regression predicted the relationship between the maturity index, represented by the FT and the physical, sound, mechanical, and chemical properties, with a correlation coefficient (R) value of 0.82 and a root mean squared error of prediction value of 1.03.