bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel mutations in the folliculin gene associated with spontaneous pneumothorax
Authors: Fröhlich B. A. , Zeitz C. , Mátyás G. , Alkadhi H. , Tuor C. , Berger W. , Russi E. W. 
Published: June 2008

Spontaneous pneumothorax is mostly sporadic but may also occur in families with genetic disorders, such as Birt–Hogg–Dubé syndrome, which is caused by mutations in the folliculin (FLCN) gene.The aim of the present study was to investigate the presence and type of mutation in a Swiss pedigree and in a sporadic case. Clinical examination, lung function tests and high-resolution computed tomography were performed. All coding exons and flanking intronic regions ofFLCNwere amplified by PCR and directly sequenced. The amount ofFLCNtranscripts was determined by quantitative real-time RT-PCR.Two novel mutations inFLCNwere identified. Three investigated family members with a history of at least one spontaneous pneumothorax were heterozygous for a single nucleotide substitution (c.779G>A) that leads to a premature stop codon (p.W260X). Quantitative real-time RT-PCR revealed a reduction ofFLCNtranscripts from the patient compared with an unaffected family member. DNA from the sporadic case carried a heterozygous missense mutation (c.394G>A). Lung function of this patient was normal and computed tomography showed similar bilateral cysts, as observed in the two members of the unrelated Swiss family.Mutations in the folliculin gene are associated with cystic lung lesions in an otherwise morphological normal lung and predispose to spontaneous pneumothorax.
International variation in prevalence of rhinitis and its relationship with sensitisation to perennial and seasonal allergens
Authors: Weinmayr G. , Forastiere F. , Weiland S. K. , Rzehak P. , Abramidze T. , Annesi-Maesano I. , Björkstén B. , Brunekreef B. , Büchele G. , Cookson W. O. C. , von Mutius E. , Pistelli R. , Strachan D. P. 
Published: June 2008

The relative importance of atopy in the aetiology of rhinitis is largely unknown. The present study investigated the geographical variations in rhinitis in relation to atopy.The cross-sectional study involved 54,178 children (aged 8–12 yrs) from 30 study centres in 22 countries worldwide. Symptoms of rhinoconjunctivitis and rhinitis without conjunctivitis in the last 12 months were reported in parental questionnaires and children were skin-prick tested.The prevalence of rhinoconjunctivitis and rhinitis without conjunctivitis varied widely (1.5–24.5% and 1.4–45.2%, respectively). For rhinoconjunctivitis, the population attributable fraction (PAF) varied 0–71% for a positive skin-prick test to one or more seasonal allergens and 0–41% for perennial allergens. The PAF for sensitisation to seasonal and perennial allergens was higher in affluent countries (36 and 25%, respectively) than nonaffluent countries (1.3 and 12.6%, respectively). For rhinitis without conjunctivitis, the PAF for perennial allergens was 8 and 4% for affluent and nonaffluent countries, respectively. No significant PAF was found for seasonal allergens.Overall, atopy explained only a limited proportion of rhinitis symptoms, suggesting that the importance of other environmental factors has been under emphasised, particularly in less affluent countries. Atopy seems to be only marginally relevant for rhinitis without conjunctivitis, which seems mainly to reflect nonatopic rhinitis.
ParaHox gene expression in larval and postlarval development of the polychaete Nereis virens(Annelida, Lophotrochozoa)
Authors: Kulakova Milana A , Cook Charles E , Andreeva Tatiana F 
Published: June 2008

Abstract

Background
Transcription factors that encode ANTP-class homeobox genes play crucial roles in determining the body plan organization and specification of different organs and tissues in bilaterian animals. The three-gene ParaHox family descends from an ancestral gene cluster that existed before the evolution of the Bilateria. All three ParaHox genes are reported from deuterostomes and lophotrochozoans, but not to date from any ecdysozoan taxa, and there is evidence that the ParaHox genes, like the related Hox genes, were ancestrally a single chromosomal cluster. However, unlike the Hox genes, there is as yet no strong evidence that the ParaHox genes are expressed in spatial and temporal order during embryogenesis.

Results
We isolated fragments of the three Nereis virens ParaHox genes, then used these as probes for whole-mount in situ hybridization in larval and postlarval worms. In Nereis virens the ParaHox genes participate in antero-posterior patterning of ectodermal and endodermal regions of the digestive tract and are expressed in some cells in the segment ganglia. The expression of these genes occurs in larval development in accordance with the position of these cells along the main body axis and in postlarval development in accordance with the position of cells in ganglia along the antero-posterior axis of each segment. In none of these tissues does expression of the three ParaHox genes follow the rule of temporal collinearity.

Conclusion
In Nereis virens the ParaHox genes are expressed during antero-posterior patterning of the digestive system (ectodermal foregut and hindgut, and endodermal midgut) of Nereis virens. These genes are also expressed during axial specification of ventral neuroectodermal cell domains, where the expression domains of each gene are re-iterated in each neuromere except for the first parapodial segment. These expression domains are probably predetermined and may be directed on the antero-posterior axis by the Hox genes, whose expression starts much earlier during embryogenesis. Our results support the hypothesis that the ParaHox genes are involved in antero-posterior patterning of the developing embryo, but they do not support the notion that these genes function only in the patterning of endodermal tissues.
Expression of cell wall related genes in basal and ear internodes of silking brown-midrib-3, caffeic acid O-methyltransferase (COMT) down-regulated, and normal maize plants
Authors: Guillaumie Sabine , Goffner Deborah , Barbier Odile , Martinant Jean-Pierre , Pichon Magalie , Barrière Yves 
Published: June 2008

Abstract

Background
Silage maize is a major forage and energy resource for cattle feeding, and several studies have shown that lignin content and structure are the determining factors in forage maize feeding value. In maize, four natural brown-midrib mutants have modified lignin content, lignin structure and cell wall digestibility. The greatest lignin reduction and the highest cell wall digestibility were observed in the brown-midrib-3 (bm3) mutant, which is disrupted in the caffeic acid O-methyltransferase (COMT) gene.

Results
Expression of cell wall related genes was investigated in basal and ear internodes of normal, COMT antisens (AS225), and bm3 maize plants of the INRA F2 line. A cell wall macro-array was developed with 651 gene specific tags of genes specifically involved in cell wall biogenesis. When comparing basal (older lignifying) and ear (younger lignifying) internodes of the normal line, all genes known to be involved in constitutive monolignol biosynthesis had a higher expression in younger ear internodes. The expression of the COMT gene was heavily reduced, especially in the younger lignifying tissues of the ear internode. Despite the fact that AS225 transgene expression was driven only in sclerenchyma tissues, COMT expression was also heavily reduced in AS225 ear and basal internodes. COMT disruption or down-regulation led to differential expressions of a few lignin pathway genes, which were all over-expressed, except for a phenylalanine ammonia-lyase gene. More unexpectedly, several transcription factor genes, cell signaling genes, transport and detoxification genes, genes involved in cell wall carbohydrate metabolism and genes encoding cell wall proteins, were differentially expressed, and mostly over-expressed, in COMT-deficient plants.

Conclusion
Differential gene expressions in COMT-deficient plants highlighted a probable disturbance in cell wall assembly. In addition, the gene expressions suggested modified chronology of the different events leading to cell expansion and lignification with consequences far beyond the phenylpropanoid metabolism. The reduced availability of monolignols and S units in bm3 or AS225 plants led to plants also differing in cell wall carbohydrate, and probably protein, composition. Thus, the deficiency in a key-enzyme of the lignin pathway had correlative effects on the whole cell wall metabolism. Furthermore, the observed differential expression between bm3 and normal plants indicated the possible involvement in the maize lignin pathway of genes which up until now have not been considered to play this role.
Induction of beta defensin 2 by NTHi requires TLR2 mediated MyD88 and IRAK-TRAF6-p38MAPK signaling pathway in human middle ear epithelial cells
Authors: Lee Haa-Yung , Takeshita Tamotsu , Shimada Jun , Akopyan Arsen , Woo Jeong-Im , Pan Huiqi , Moon Sung K , Andalibi Ali , Park Rae-Kil , Kang Sung-Ho , Kang Shin-Seok , Gellibolian Robert , Lim David J 
Published: June 2008

Abstract

Background
All mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against various otitis media pathogens. Among the AIIMs, human β-defensin 2 is the most potent molecule and is inducible by exposure to inflammatory stimuli such as bacterial components or proinflammatory cytokines. Even though the β-defensin 2 is an important AIIM, the induction mechanism of this molecule has not been clearly established. We believe that this report is the first attempt to elucidate NTHi induced β-defensin expression in airway mucosa, which includes the middle ear.

Methods
Monoclonal antibody blocking method was employed in monitoring the TLR-dependent NTHi response. Two gene knock down methods – dominant negative (DN) plasmid and small interfering RNA (siRNA) – were employed to detect and confirm the involvement of several key genes in the signaling cascade resulting from the NTHi stimulated β-defensin 2 expression in human middle ear epithelial cell (HMEEC-1). The student's t-test was used for the statistical analysis of the data.

Results
The experimental results showed that the major NTHi-specific receptor in HMEEC-1 is the Toll-like receptor 2 (TLR2). Furthermore, recognition of NTHi component(s)/ligand(s) by TLR2, activated the Toll/IL-1 receptor (TIR)-MyD88-IRAK1-TRAF6-MKK3/6-p38 MAPK signal transduction pathway, ultimately leading to the induction of β-defensin 2.

Conclusion
This study found that the induction of β-defensin 2 is highest in whole cell lysate (WCL) preparations of NTHi, suggesting that the ligand(s) responsible for this up-regulation may be soluble macromolecule(s). We also found that this induction takes place through the TLR2 dependent MyD88-IRAK1-TRAF6-p38 MAPK pathway, with the primary response occurring within the first hour of stimulation. In combination with our previous studies showing that IL-1α-induced β-defensin 2 expression takes place through a MyD88-independent Raf-MEK1/2-ERK MAPK pathway, we found that both signaling cascades act synergistically to up-regulate β-defensin 2 levels. We propose that this confers an essential evolutionary advantage to the cells in coping with infections and may serve to amplify the innate immune response through paracrine signaling.
Deferiprone targets aconitase: Implication for Friedreich's ataxia treatment
Authors: Goncalves Sergio , Paupe Vincent , Dassa Emmanuel P , Rustin Pierre 
Published: June 2008

Abstract

Background
Friedreich ataxia is a neurological disease originating from an iron-sulfur cluster enzyme deficiency due to impaired iron handling in the mitochondrion, aconitase being particularly affected. As a mean to counteract disease progression, it has been suggested to chelate free mitochondrial iron. Recent years have witnessed a renewed interest in this strategy because of availability of deferiprone, a chelator preferentially targeting mitochondrial iron.

Method
Control and Friedreich's ataxia patient cultured skin fibroblasts, frataxin-depleted neuroblastoma-derived cells (SK-N-AS) were studied for their response to iron chelation, with a particular attention paid to iron-sensitive aconitase activity.

Results
We found that a direct consequence of chelating mitochondrial free iron in various cell systems is a concentration and time dependent loss of aconitase activity. Impairing aconitase activity was shown to precede decreased cell proliferation.

Conclusion
We conclude that, if chelating excessive mitochondrial iron may be beneficial at some stage of the disease, great attention should be paid to not fully deplete mitochondrial iron store in order to avoid undesirable consequences.
ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression
Authors: Fritzsche Florian R , Wassermann Kirsten , Jung Monika , Tölle Angelika , Kristiansen Ilka , Lein Michael , Johannsen Manfred , Dietel Manfred , Jung Klaus , Kristiansen Glen 
Published: June 2008

AbstractBackgroundA DisintegrinAndMetalloprotease (ADAM) 9 has been implicated in tumour progression of various solid tumours, however, little is known about its role in renal cell carcinoma. We evaluated the expression of ADAM9 on protein and transcript level in a clinico-pathologically characterized renal cell cancer cohort.Methods108 renal cancer cases were immunostained for ADAM9 on a tissue-micro-array. For 30 additional cases, ADAM9 mRNA of microdissected tumour and normal tissue was analyzed via quantitative RT-PCR. SPSS 14.0 was used to apply crosstables (Fisher's exact test and χ2-test), correlations and univariate as well as multivariate survival analyses.ResultsADAM9 was significantly up-regulated in renal cancer in comparison to the adjacent normal tissue on mRNA level. On protein level, ADAM9 was significantly associated with higher tumour grade, positive nodal status and distant metastasis. Furthermore, ADAM9 protein expression was significantly associated with shortened patient survival in the univariate analysis.ConclusionADAM9 is strongly expressed in a large proportion of renal cell cancers, concordant with findings in other tumour entities. Additionally, ADAM9 expression is significantly associated with markers of unfavourable prognosis. Whether the demonstrated prognostic value of ADAM9 is independent from other tumour parameters will have to be verified in larger study cohorts.
Physician and patient attitudes towards complementary and alternative medicine in obstetrics and gynecology
Authors: Furlow Mandi L , Patel Divya A , Sen Ananda , Liu J Rebecca 
Published: June 2008

Abstract

Background
In the U.S., complementary and alternative medicine (CAM) use is most prevalent among reproductive age, educated women. We sought to determine general attitudes and approaches to CAM among obstetric and gynecology patients and physicians.

Methods
Obstetrician-gynecologist members of the American Medical Association in the state of Michigan and obstetric-gynecology patients at the University of Michigan were surveyed. Physician and patient attitudes and practices regarding CAM were characterized.

Results
Surveys were obtained from 401 physicians and 483 patients. Physicians appeared to have a more positive attitude towards CAM as compared to patients, and most reported routinely endorsing, providing or referring patients for at least one CAM modality. The most commonly used CAM interventions by patients were divergent from those rated highest among physicians, and most patients did not consult with a health care provider prior to starting CAM.

Conclusion
Although obstetrics/gynecology physicians and patients have a positive attitude towards CAM, physician and patients' view of the most effective CAM therapies were incongruent. Obstetrician/gynecologists should routinely ask their patients about their use of CAM with the goal of providing responsible, evidence-based advice to optimize patient care.
Factors associated with the subspecialty choices of internal medicine residents in Canada
Authors: Horn Leora , Tzanetos Katina , Thorpe Kevin , Straus Sharon E 
Published: June 2008

Abstract

Background
Currently, there are more residents enrolled in cardiology training programs in Canada than in immunology, pharmacology, rheumatology, infectious diseases, geriatrics and endocrinology combined. There is no published data regarding the proportion of Canadian internal medicine residents applying to the various subspecialties, or the factors that residents consider important when deciding which subspecialty to pursue. To address the concern about physician imbalances in internal medicine subspecialties, we need to examine the factors that motivate residents when making career decisions.

Methods
In this two-phase study, Canadian internal medicine residents participating in the post graduate year 4 (PGY4) subspecialty match were invited to participate in a web-based survey and focus group discussions. The focus group discussions were based on issues identified from the survey results. Analysis of focus group transcripts grew on grounded theory.

Results
110 PGY3 residents participating in the PGY4 subspecialty match from 10 participating Canadian universities participated in the web-based survey (54% response rate). 22 residents from 3 different training programs participated in 4 focus groups held across Canada. Our study found that residents are choosing careers that provide intellectual stimulation, are consistent with their personality, and that provide a challenge in diagnosis. From our focus group discussions it appears that lifestyle, role models, mentorship and the experience of the resident with the specialty appear to be equally important in career decisions. Males are more likely to choose procedure based specialties and are more concerned with the reputation of the specialty as well as the anticipated salary. In contrast, residents choosing non-procedure based specialties are more concerned with issues related to lifestyle, including work-related stress, work hours and time for leisure as well as the patient populations they are treating.

Conclusion
This study suggests that internal medicine trainees, and particularly males, are increasingly choosing procedure-based specialties while non-procedure based specialties, and in particular general internal medicine, are losing appeal. We need to implement strategies to ensure positive rotation experiences, exposure to role models, improved lifestyle and job satisfaction as well as payment schedules that are equitable between disciplines in order to attract residents to less popular career choices.
Polymorphism patterns in Duffy-binding protein among Thai Plasmodium vivax isolates
Authors: Gosi Panita , Khusmith Srisin , Khalambaheti Thareerat , Lanar David E , Schaecher Kurt E , Fukuda Mark M , Miller Scott R 
Published: June 2008

Abstract

Background
The Duffy-binding protein II of Plasmodium vivax (PvDBPII) has been considered as an attractive target for vaccine-mediated immunity despite a possible highly polymorphic nature. Among seven PvDBP domains, domain II has been shown to exhibit a high rate of nonsynonymous polymorphism, which has been suggested to be a potential immune (antibody binding) evasion mechanism. This study aimed to determine the extent of genetic polymorphisms and positive natural selection at domain II of the PvDBP gene among a sampling of Thai P. vivax isolates.

Methods
The PvDBPII gene was PCR amplified and the patterns of polymorphisms were characterized from 30 Thai P. vivax isolates using DNA cloning and sequencing. Phylogenetic analysis of the sequences and positive selection were done using DnaSP ver 4.0 and MEGA ver 4.0 packages.

Results
This study demonstrated a high rate of nonsynonymous polymorphism. Using Sal I as the reference strain, a total of 30 point-mutations were observed in the PvDBPII gene among the set of Thai P. vivax isolates, of which 25 nonsynonymous and five synonymous were found. The highest frequency of polymorphism was found in five variant amino acids (residues D384G, R390H, L424I, W437R, I503K) with the variant L424I having the highest frequency. The difference between the rates of nonsynonymous and synonymous mutations estimated by the Nei and Gojobori's method suggested that PvDBPII antigen appears to be under selective pressure. Phylogenetic analysis of PvDBPII Thai P. vivax isolates to others found internationally demonstrated six distinct allele groups. Allele groups 4 and 6 were unique to Thailand.

Conclusion
Polymorphisms within PvDBPII indicated that Thai vivax malaria parasites are genetically diverse. Phylogenetic analysis of DNA sequences using the Neighbour-Joining method demonstrated that Thai isolates shared distinct alleles with P. vivax isolates from different geographical areas. The study reported here will be valuable for the development of PvDBPII-based malaria vaccine.
Laugh syncope as a rare sub-type of the situational syncopes: a case report
Authors: Nishida Katsufumi , Hirota Sean K , Tokeshi Jinichi 
Published: June 2008

Abstract

Introduction
Laughter is a good medicine; it enhances cardiovascular health and the immune system. What happens, however, if a person laughs too much or the laughter becomes out of control? Laughter-induced syncope is rare and likely goes unrecognized by many health care providers. It is thought to be another form of Valsalva-induced syncope.

Case presentation
We report the case of a 56-year-old, moderately obese (body mass index of 35) man with a past medical history of sleep apnea, hypertension and hyperlipidemia who suffered from syncope secondary to intense laughter. The patient also had a history of syncope in the distant past when he collapsed on the floor for several seconds. Treadmill stress testing after the incident revealed no arrhythmia or ischemic disease, although he complained of dizziness after the test and a sudden drop in blood pressure was noted.

Conclusion
Laughter-induced or gelastic syncope is extremely rare. It is thought to be a sub-type of the situational syncopes.
Protecting Privacy Using k-Anonymity
Authors: El Emam Khaled , Dankar Fida Kamal 
Published: June 2008

AbstractObjective: There is increasing pressure to share health information and even make it publicly available. However, such disclosures of personal health information raise serious privacy concerns. To alleviate such concerns, it is possible to anonymize the data before disclosure. One popular anonymization approach is k-anonymity. There have been no evaluations of the actual re-identification probability of k-anonymized data sets.Design: Through a simulation, we evaluated the re-identification risk of k-anonymization and three different improvements on three large data sets.Measurement: Re-identification probability is measured under two different re-identification scenarios. Information loss is measured by the commonly used discernability metric.Results: For one of the re-identification scenarios, k-Anonymity consistently over-anonymizes data sets, with this over-anonymization being most pronounced with small sampling fractions. Over-anonymization results in excessive distortions to the data (i.e., high information loss), making the data less useful for subsequent analysis. We found that a hypothesis testing approach provided the best control over re-identification risk and reduces the extent of information loss compared to baseline k-anonymity.Conclusion: Guidelines are provided on when to use the hypothesis testing approach instead of baseline k-anonymity.