bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitomycin C-treated dendritic cells inactivate autoreactive T cells: Toward the development of a tolerogenic vaccine in autoimmune diseases
Authors: Terness Peter , Oelert Thilo , Ehser Sandra , Chuang Jing Jing , Lahdou Imad , Kleist Christian , Velten Florian , Hämmerling Günter J. , Arnold Bernd , Opelz Gerhard
Published: November 2008

Treatment of autoimmune diseases remains a challenge for immunological research. An ideal therapy should inhibit the immune reaction against the diseased organ and leave the rest of the immune response intact. Our previous studies showed that donor-derived dendritic cells (DCs) treated
in vitro
with mitomycin C (MMC) suppress rat heart allograft rejection if injected into recipients before transplantation. Here we analyze their efficacy in controlling autoimmunity. MMC-DCs loaded with myelin-basic-protein (MBP) inhibited specific T cells derived from multiple sclerosis patients
in vitro
. If coincubated with MMC-DCs, T cells were arrested in the G
0
/G
1
cell cycle phase. Microarray gene scan showed that MMC influences the expression of 116 genes in DCs, one main cluster comprising apoptotic and the second cluster immunosuppressive genes. Apparently, the combination of apoptosis with expression of tolerogenic molecules renders MMC-DCs suppressive. MBP-loaded MMC-DCs also inhibited mouse T cells
in vitro
and, in contrast to MBP-loaded naïve DCs, did not induce experimental autoimmune encephalitis. Most importantly, mice vaccinated with inhibitory DCs became resistant to the disease. Whereas this is not the first report on generation of suppressive DCs, it delineates a method using a clinically approved drug at nontoxic concentrations, which yields irreversibly changed DCs, effective across species
in vitro
and
in vivo
.
An endothelin-1 switch specifies maxillomandibular identity
Authors: Sato Takahiro , Kurihara Yukiko , Asai Rieko , Kawamura Yumiko , Tonami Kazuo , Uchijima Yasunobu , Heude Eglantine , Ekker Marc , Levi Giovanni , Kurihara Hiroki
Published: November 2008

Articulated jaws are highly conserved structures characteristic of gnathostome evolution. Epithelial-mesenchymal interactions within the first pharyngeal arch (PA1) instruct cephalic neural crest cells (CNCCs) to form the different skeletal elements of the jaws. The endothelin-1 (Edn1)/endothelin receptor type-A (Ednra)→Dlx5/6→Hand2 signaling pathway is necessary for lower jaw formation. Here, we show that the Edn1 signaling is sufficient for the conversion of the maxillary arch to mandibular identity. Constitutive activation of Ednra induced the transformation of upper jaw, maxillary, structures into lower jaw, mandibular, structures with duplicated Meckel's cartilage and dermatocranial jaws constituted by 4 dentary bones. Misexpression of
Hand2
in the Ednra domain caused a similar transformation. Skeletal transformations are accompanied by neuromuscular remodeling. Ednra is expressed by most CNCCs, but its constitutive activation affects predominantly PA1. We conclude that after migration CNCCs are not all equivalent, suggesting that their specification occurs in sequential steps. Also, we show that, within PA1, CNCCs are competent to form both mandibular and maxillary structures and that an Edn1 switch is responsible for the choice of either morphogenetic program.
Structure of macrophage colony stimulating factor bound to FMS: Diverse signaling assemblies of class III receptor tyrosine kinases
Authors: Chen Xiaoyan , Liu Heli , Focia Pamela J. , Shim Ann Hye-Ryong , He Xiaolin
Published: November 2008

Macrophage colony stimulating factor (M-CSF), through binding to its receptor FMS, a class III receptor tyrosine kinase (RTK), regulates the development and function of mononuclear phagocytes, and plays important roles in innate immunity, cancer and inflammation. We report a 2.4 Å crystal structure of M-CSF bound to the first 3 domains (D1–D3) of FMS. The ligand binding mode of FMS is surprisingly different from KIT, another class III RTK, in which the major ligand-binding domain of FMS, D2, uses the CD and EF loops, but not the β-sheet on the opposite side of the Ig domain as in KIT, to bind ligand. Calorimetric data indicate that M-CSF cannot dimerize FMS without receptor-receptor interactions mediated by FMS domains D4 and D5. Consistently, the structure contains only 1 FMS-D1–D3 molecule bound to a M-CSF dimer, due to a weak, hydrophilic M-CSF:FMS interface, and probably a conformational change of the M-CSF dimer in which binding to the second site is rendered unfavorable by FMS binding at the first site. The partial, intermediate complex suggests that FMS may be activated in two steps, with the initial engagement step distinct from the subsequent dimerization/activation step. Hence, the formation of signaling class III RTK complexes can be diverse, engaging various modes of ligand recognition and various mechanistic steps for dimerizing and activating receptors.
Sortase A localizes to distinct foci on the
Streptococcus pyogenes
membrane
Authors: Raz Assaf , Fischetti Vincent A.
Published: November 2008

Cell wall peptidoglycan-anchored surface proteins are essential virulence factors in many gram-positive bacteria. The attachment of these proteins to the peptidoglycan is achieved through a transpeptidation reaction, whereby sortase cleaves a conserved C-terminal LPXTG motif and covalently attaches the protein to the peptidoglycan precursor lipid II. It is unclear how the sorting reaction is regulated spatially and what part sortase localization plays in determining the distribution of surface proteins. This is mainly the result of inadequate immunofluorescence techniques required to resolve these issues in certain bacterial pathogens. Here we describe the utilization of the phage lysin PlyC to permeabilize the cell wall of
Streptococcus pyogenes
to antibodies, thereby allowing the localization of sortase A using deconvolution immunofluorescence microscopy. We find that sortase localizes within distinct membranal foci, the majority of which are associated with the division septum and colocalize with areas of active M protein anchoring. Sortase distribution to the new septum begins at a very early stage, culminates during septation, and decays after division is completed. This implies that the sorting reaction is a dynamic, highly regulated process, intimately associated with cell division. The ability to study cytoplasmic and membrane antigens using deconvolution immunofluorescence microscopy will facilitate further study of cellular processes in
S. pyogenes
.
Fear of failure: Are we doing too many trials of instrumental delivery in theatre?
Authors: EBULUE VINCENT , VADALKAR JUHIE , CELY SANDRA , DOPWELL FADILA , YOONG WAI
Published: November 2008

Objectives. Cesarean section has largely replaced the role of difficult midcavity instrumental deliveries. The aim of this study was to determine the trend in trials of instrumental delivery as well as the maternal and fetal factors associated with successful and failed trial of instrumental deliveries. Setting. North Middlesex University Hospital, a teaching hospital in London. Study design. A retrospective review of trials of instrumental delivery in theatre involving singleton term pregnancies between 2000 and 2005. Results. Of the 114 trials, 82 (40 forceps and 42 vacuum extraction) were successful. Women who had successful trials were similar in age (27.8±5.9 vs. 27.1±5.4 yrs), gestation (40.5±2.1 vs. 40.5±1.1 wks) and parity (0.4±1.2 vs. 0.3±1.6) when compared to those who were unsuccessful (p>0.05). The two groups also had similar birth weight (3.6±0.7 vs. 3.7±0.4 kg) and duration of second stage (164.9±12.0 vs. 162.8±16.0 min) (p>0.05). Babies born following failed trial of instrumental deliveries were more likely to be acidotic (p = 0.014) but admission to Special Care Baby Unit was similar in both groups. Women who had failed trials of instrumental delivery were more likely to have post‐partum hemorrhage (802.7±100.0 vs. 425.4±120.0 ml) and pyrexia (15.6% vs. 6.1%) (p<0.05). Trial of instrumental delivery was twice as likely to fail if occipito‐posterior and three times more likely to succeed if the presenting part was visible (p<0.05). However, 25% of babies had presenting parts well below the ischial spines but still had instrumental deliveries in theatre and 80% of this subgroup were delivered by junior trainees. Although 71.9% of trials of instrumental delivery were successful, many were relatively uncomplicated and did not necessarily require delivery in theatre. Conclusion. Unsuccessful trials are associated with maternal rather than neonatal morbidity. The shortening of duration training as well as reduction of working hours in the United Kingdom has led to obstetric trainees being less experienced in conducting instrumental deliveries. Thus, many junior trainees may prefer to conduct relatively uncomplicated instrumental deliveries in theatre. Appropriate training and senior staff input would help reduce this.
Motif Tool Manager: a web-based framework for motif discovery
Authors: Phan Vinhthuy , Furlotte Nicholas A.
Published: November 2008

Motivation: Motif Tool Manager is a web-based framework for comparing and combining different approaches to discover novel DNA motifs. It comes with a set of five well-known approaches to motif discovery. It provides an easy mechanism for adding new motif finding tools to the framework through a web-interface and a minimal setup of the tools on the server. Users can execute the tools through the web-based framework and compare results from such executions. The framework provides a basic mechanism for identifying the most similar motif candidates found by a majority of themotif finding tools.

Availability:  http://cetus.cs.memphis.edu/motif

Contact:  vphan@memphis.edu
Bag of Peaks: interpretation of NMR spectrometry
Authors: Brelstaff Gavin , Bicego Manuele , Culeddu Nicola , Chessa Matilde
Published: November 2008

Motivation: The analysis of high-resolution proton nuclear magnetic resonance (NMR) spectrometry can assist human experts to implicate metabolites expressed by diseased biofluids. Here, we explore an intermediate representation, between spectral trace and classifier, able to furnish a communicative interface between expert and machine. This representation permits equivalent, or better, classification accuracies than either principal component analysis (PCA) or multi-dimensional scaling (MDS). In the training phase, the peaks in each trace are detected and clustered in order to compile a common dictionary, which could be visualized and adjusted by an expert. The dictionary is used to characterize each trace with a fixed-length feature vector, termed Bag of Peaks, ready to be classified with classical supervised methods.

Results: Our small-scale study, concerning Type I diabetes in Sardinian children, provides a preliminary indication of the effectiveness of the Bag of Peaks approach over standard PCA and MDS. Consistently, higher classification accuracies are obtained once a sufficient number of peaks (>10) are included in the dictionary. A large-scale simulation of noisy spectra further confirms this advantage. Finally, suggestions for metabolite-peak loci that may be implicated in the disease are obtained by applying standard feature selection techniques.

Availability: Matlab code to compute the Bag of Peaks representation may be found at http://economia.uniss.it/docenti/bicego/BagOfPeaks/BagOfPeaks.zip

Contact:  gjb@crs4.it
Characterising deindustrialisation: An analysis of changes in manufacturing employment and output internationally
Authors: Tregenna Fiona
Published: November 2008

Deindustrialisation is typically conceptualised as a decline in manufacturing as a share of total employment. From a Kaldorian perspective deindustrialisation could have negative implications for long-run growth, given the special growth-pulling properties of manufacturing. However, defining deindustrialisation purely in terms of employment share is conceptually limiting given that some of the Kaldorian processes operate primarily through output rather than employment, as well as blunting empirical analysis by not focussing enough on changes in manufacturing share of gross domestic product (GDP). This study develops a new method using decomposition techniques to analyse changes in manufacturing employment levels and shares in 48 countries over periods of ‘deindustrialisation’. The analysis separates out changes in the levels and shares of employment manufacturing into components associated with changes in the share of manufacturing in GDP, the growth of manufacturing value-added, the labour intensity of manufacturing production and economic growth. The results indicate that in most cases the decline in manufacturing employment is associated primarily with falling labour intensity of manufacturing rather than an overall decline in the size or share of the manufacturing sector. We suggest that deindustrialisation should appropriately be defined in terms of a sustained decline in both the share of manufacturing in total employment and the share of manufacturing in GDP.
Self‐Ratings of Olfactory Function Reflect Odor Annoyance Rather than Olfactory Acuity
Authors: Knaapila Antti , Tuorila Hely , Kyvik Kirsten O. , Wright Margaret J. , Keskitalo Kaisu , Hansen Jonathan , Kaprio Jaakko , Perola Markus , Silventoinen Karri
Published: November 2008

Objective/Hypothesis: Self‐ratings of olfactory function often correlates poorly with results of objective smell tests. We explored these ratings relative to self‐rating of odor annoyance, to odor identification ability, and to mean perceived intensity of odors, and estimated relative genetic and environmental contributions to these traits.

Participants and Methods: A total of 1,311 individual twins from the general population (62% females and 38% males, aged 10–83 years, mean age 29 years) including 191 monozygous and 343 dizygous complete twin pairs from Australia, Denmark, Finland, and the United Kingdom rated their sense of smell and annoyance caused by ambient smells (e.g., smells of foods) using seven categories, and performed odor identification and evaluation task for six scratch‐and‐sniff odor stimuli.

Results: The self‐rating of olfactory function correlated with the self‐rating of odor annoyance (r = 0.30) but neither correlated with the odor identification score. Quantitative genetic modeling revealed no unambiguously significant genetic contribution to variation in any of the studied traits.

Conclusion: The results suggest that environmental rather than genetic factors modify the self‐rating of olfactory function and support earlier findings of discrepancy between subjective and objective measures of olfactory function. In addition, the results imply that the self‐rating of olfactory function arises from experienced odor annoyance rather than from actual olfactory acuity.
Anatomical Changes of the Ethmoid Cavity After Endoscopic Sinus Surgery
Authors: Platt Michael P. , Cunnane Mary E. , Curtin Hugh D. , Metson Ralph
Published: November 2008

Objective: Alteration of the bony architecture of the sinus cavities has been observed in chronic sinusitis. Plasticity of the ethmoid sinus framework after endoscopic surgery, however, is a newly described entity. The objective of this study was to determine the incidence and extent of changes in ethmoid size after ethmoidectomy.

Study Design: Retrospective review performed at an academic medical center.

Methods: Computed tomography scans performed from 2006 through 2007 at the Massachusetts Eye and Ear Infirmary (n = 5,131) were reviewed to identify 100 consecutive patients who underwent sinus surgery and met inclusion criteria. Seven dimensions were measured for each pre‐ and postoperative scan (n = 200) using Voxar 3D software.

Results: Computed tomography scans performed before and 2 to 37 months after ethmoidectomy demonstrated a decrease of 1.1 ± 1.6 mm in mean ethmoid cavity width at the level of the cribriform plate and posterior globe after surgery (P < .0001). Twenty‐five patients (25%) had >1 mm decrease in mean ethmoid width, and six patients (6%) had a decrease of >2 mm (mean 3.1 ± 0.9 mm). These findings seemed to be the result of postoperative bowing of the medial ethmoid walls with a corresponding increase in orbital volume. These volumetric changes resulted in a postoperative subclinical retrodisplacement (enophthalmos) of the globes (mean 0.2 ± 0.8 mm, P = .008). The extent of surgery, including performance of frontal recess dissection (P = .007) and total ethmoidectomy (P = .021) were found to be independent predictors of the observed changes in sinus dimensions.

Conclusions: Postsurgical plasticity of the ethmoid cavity is a new concept supported by observed changes in sinus dimensions after ethmoidectomy. These changes may reflect a loss of internal structural support and forces of contracture during the postoperative healing period.
Transoral Robotic Surgery Using a Carbon Dioxide Flexible Laser for Tumors of the Upper Aerodigestive Tract
Authors: Desai Shaun C. , Sung Chih‐Kwang , Jang David W. , Genden Eric M.
Published: November 2008

Objective: To determine the safety, feasibility, and efficacy of coupling transoral robotic technology with the flexible carbon dioxide (CO2) laser for various tumors of the oropharynx and supraglottic larynx.

Study Design: Prospective, pilot trial.

Methods: Eight patients were enrolled in an IRB‐approved prospective trial for transoral robotic surgery with the aid of the flexible CO2 laser.

Results: Seven male patients with early carcinoma of the oropharynx or larynx successfully underwent tumor extirpation with the transoral robot and the flexible CO2 laser. We were unable to gain access to the supraglottic larynx in one female patient. The final pathology revealed seven patients with squamous cell carcinoma and one patient with adenoid cystic carcinoma. The flexible CO2 laser provided fine incisions with excellent hemostasis and minimal peripheral tissue injury. Additionally, the laser provided an excellent tool for raising pharyngeal flaps for reconstruction of the oropharynx.

Conclusion: The flexible CO2 laser offers a unique advantage of precise incisions and may provide a valuable tool for both tumor extirpation and the creation of flaps for transoral robotic reconstruction.
Changes of Extremity and Laryngeal Muscle Electromyographic Amplitudes After Intravenous Administration of Vecuronium
Authors: Shi Yongbing , Hou Vivian , Tucker Anne , Cohen James
Published: November 2008

Objectives: To compare electromyographic (EMG) amplitude changes in extremity and laryngeal muscles after vecuronium administration and study the effects of topical lidocaine on laryngeal EMG in a swine model.

Study Design: Prospective animal study.

Methods: Electrically evoked EMG activities were recorded from the vocalis muscles (directly and via an EMG endotracheal tube) and from the flexor digitorum muscles before and after intravenous vecuronium administration. EMG amplitudes were followed for 30 minutes after vecuronium injection together with monitoring of limb twitches to train‐of‐four stimulation. The testing was repeated after a 30‐minute wash‐out period and with topical lidocaine.

Results: EMG amplitude recovery occurred sooner and more quickly in flexor digitorum muscle than in vocalis muscles. Reappearance of four twitches corresponded to EMG amplitude recovery to about 80% of the baseline in flexor digitorum muscles and to about half‐baseline size in vocalis muscles. EMG amplitudes were generally lower at the start of the second round testing than the first round, with somewhat slower recovery in vocalis muscles.

Conclusions: In contrast to reports by others in human studies, extremity muscles seem to be more resistant to vecuronium at 0.1 mg/kg than laryngeal muscles in the swine. Reappearance of four twitches corresponds to 50% of laryngeal EMG recovery and indicates adequate condition for monitoring electrically evoked laryngeal EMG activities. This study is inconclusive regarding the effects of topically applied lidocaine on laryngeal EMG amplitudes. Translation of these data to humans should be done with caution.
Predictors of Olfactory Dysfunction in Patients With Chronic Rhinosinusitis
Authors: Litvack Jamie R. , Fong Karen , Mace Jess , James Kenneth E. , Smith Timothy L.
Published: November 2008

Objectives: To measure the prevalence of and identify clinical characteristics associated with poor olfactory function in a large cohort of patients with chronic rhinosinusitis (CRS).

Study Design: Multi‐institutional, cross sectional analysis.

Methods: An objective measure of olfactory dysfunction, the Smell Identification Test, demographic data, clinical factors, and comorbidity data were collected from a cohort of 367 patients who presented with CRS at three tertiary care centers. Data were analyzed using univariate and multivariate analyses.

Results: Sixty‐four percent of men and women aged 18 to 64 had olfactory dysfunction whereas 95% of patients older than or equal to 65 years had olfactory dysfunction (P < .001); no significant difference was noted by gender. By multivariate logistic regression analysis, patients with nasal polyposis [Odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3–4.2, P = .003] and patients older than or equal to 65 years (OR 10.0, 95% CI 2.3–43.7, P = .002) were at increased risk of hyposmia. Patients with nasal polyposis (OR 13.2, 95% CI 5.7–30.7, P < .001), asthma (OR 4.2, 95% CI 1.8–9.8, P = .001), older than or equal to 65 years (OR 15.6, 95% CI 2.3–104.9, P = .005), and smokers (OR 7.6, 95% CI 1.8–31.6, P = .005) were at increased risk of anosmia.

Conclusions: Poor olfactory function is common in patients with CRS. Age, nasal polyposis, smoking, and asthma were significantly associated with olfactory dysfunction in patients with CRS. Neither prior endoscopic sinus surgery nor a history of allergic rhinitis was associated with olfactory dysfunction. Septal deviation and inferior turbinate hypertrophy were associated with normal olfactory function.
Palatal Flap Modifications Allow Pedicled Reconstruction of the Skull Base
Authors: Oliver Christopher L. , Hackman Trevor G. , Carrau Ricardo L. , Snyderman Carl H. , Kassam Amin B. , Prevedello Daniel M. , Gardner Paul
Published: November 2008

Objectives: Defects after endoscopic expanded endonasal approaches (EEA) to the skull base, have exposed limitations of traditional reconstructive techniques. The ability to adequately reconstruct these defects has lagged behind the ability to approach/resect lesions at the skull base. The posteriorly pedicled nasoseptal flap is our primary reconstructive option; however, prior surgery or tumors can preclude its use. We focused on the branches of the internal maxillary artery, to develop novel pedicled flaps, to facilitate the reconstruction of defects encountered after skull base expanded endonasal approaches.

Study Design: Feasibility.

Methods: We reviewed radiology images with attention to the pterygopalatine fossa and the descending palatine vessels (DPV), which supply the palate. Using cadaver dissections, we investigated the feasibility of transposing the standard mucoperiosteal palatal flap into the nasal cavity and mobilizing the DPV for pedicled skull base reconstruction.

Results: We transposed the palate mucoperiosteum into the nasal cavity through limited enlargement of a single greater palatine foramen. Our method preserves the integrity of the nasal floor mucosa, and mobilizes the DPV from the greater palatine foramen to their origin in the pterygopalatine fossa. Radiological measurements and cadevaric dissections suggest that the transposed, pedicled palatal flap (the Oliver pedicled palatal flap) could be used to reconstruct defects of the planum, sella, and clivus.

Conclusions: Our novel modifications to the island palatal flap yield a large (12–18 cm2) mucoperiosteal flap based on a ∼ 3 cm pedicle. The Oliver pedicled palatal flap shows potential for nasal cavity and skull base reconstruction (see video, available online only).
Papillary Thyroid Cancer: Controversies in the Management of Neck Metastasis
Authors: Davidson H Carter , Park Brian J. , Johnson Jonas T.
Published: November 2008

Objective/Hypothesis: To describe our institution's experience with the management of cervical metastasis in papillary thyroid carcinoma (PTC) and suggest a treatment strategy based on the incidence of pathologic nodes and cervical recurrence in patients undergoing varied surgical approaches to address lymphadenopathy over the study dates.

Materials and Methods: Between December 1, 1972 and September 1, 2007, 183 total patients diagnosed with PTC at the University of Pittsburgh Medical Center were treated with lymphadenectomy. Pathologic parameters, including number of pathologic nodes and extent of lymphadenectomy were correlated to disease recurrence.

Study Design: Retrospective chart review.

Results: The incidence of pathologic nodes in lymphadenectomy specimens (57.9%) and the recurrence rate (33.7%) were high, in our study population. In comparing techniques with address lymphadenopathy, the highest recurrence rate was observed in patients with pathologic nodes treated with “lymph node plucking” procedures at the time of thyroidectomy and those patients with multiple nodes involved. Few patients with no pathologic nodes, regardless of lymphadenectomy extent recurred.

Conclusions: Our data show that limited neck dissection and disease burden are associated with the highest rates of cervical recurrence in regional metastatic PTC. Comprehensive functional neck dissection would seem to offer the patient the best opportunity for control of cervical metastasis. The American Thyroid Association recommends thyroglobulin monitoring and ultrasound evaluation of the neck in all postoperative patients. Therefore patients with the diagnosis of papillary thyroid cancer need preoperative ultrasound of the lateral neck and fine needle aspiration of suspicious nodes to avoid undertreating patients scheduled for total thyroidectomy. Neck dissection of the compartments in which pathologic nodes were detected (central, lateral, or both) should then be undertaken at the time of initial thyroidectomy. Eliminating all disease remains elusive and the prognosticsignificance of cervical disease persistence and recurrence is still unknown. Patients with cervical metastasis are at substantial risk of regional recurrence, necessitating repeat surgery. Parathyroid implantation should be considered at the time of the initial surgery to reduce the risk of hypoparathyroidism should subsequent procedures be required. More information will be necessary to better understand the prognostic significance of these regional metastases. In the interim, many patients may be overtreated, whereas some remain at risk of death because of disease.
The GNAS1 T393C Polymorphism Predicts Survival in Patients With Advanced Squamous Cell Carcinoma of the Larynx
Authors: Lehnerdt Goetz F. , Franz Peter , Winterhoff Sebastian , Bankfalvi Agnes , Grehl Sara , Lang Stephan , Schmid Kurt W. , Siffert Winfried , Jahnke Klaus , Frey Ulrich H.
Published: November 2008

Objectives/Hypothesis: In previous studies, we have demonstrated that the T‐allele of a specific single nucleotide polymorphism (SNP) in the Gαs gene (T393C) correlates with increased Gαs expression and hence apoptosis. The T‐allele was associated with a favorable outcome in a variety of human cancers, for example, carcinoma of the urinary bladder, kidney, colorectal, oro‐ and hypopharynx.

Study Design: The prognostic value of the T393C SNP was retrospectively evaluated in an unselected series of patients treated with curative intent for laryngeal squamous cell carcinomas including all tumor stages with different therapeutic regimens.

Methods: DNA analysis was performed using DNA from paraffin‐embedded tissue samples from 157 patients (142 men, 15 women) with a median follow‐up of 68 (3–143) months. The various genotypes were correlated with the overall survival.

Results: Survival was significantly dependent on the T393C genotype in advanced American Joint Committee on Cancer (AJCC) stages (III–IV) with an apparent gene‐dose effect (P = .0437). Five‐year survival rates were 76% for TT, 49% for TC, and 43.5% for CC. In multivariate analysis including age at diagnosis, AJCC stage, grade, gender, and T393C genotypes, patients with CC genotype displayed a higher risk for death with a hazard ratio of 2.59 (95% confidence interval: 1.01–6.64, P = .047) compared with the reference group consisting of T393 homozygous individuals.

Conclusions: The T393C SNP is a prognostic marker that could help to identify high risk patients suffering from head and neck cancer.
The Therapeutic Effect of OK‐432 (Picibanil) Sclerotherapy for Benign Neck Cysts
Authors: Kim Myung Gu , Kim Sun Gon , Lee Jun Ho , Eun Young Gyu , Yeo Seung Geun
Published: November 2008

Background and Objectives: In general, benign neck cysts are treated by surgical excision. This can present technical difficulties and frequent recurrences, because of insufficient surgery. Sclerosing agents such as OK‐432 have been tested for the nonsurgical treatment of these cysts. We have assessed the efficacy of OK‐432 sclerotherapy for benign neck cysts.

Materials and Methods: The study group consisted of 75 patients (42 men, 33 women) diagnosed with and treated for benign neck cysts between March 2001 and December 2007 by intralesional injection of OK‐432. The liquid content of each cyst was aspirated as much as possible, and the same volume of OK‐432 solution was injected. Patients were assessed by ultrasonography or computerized tomography, and therapeutic outcomes and adverse effects were evaluated by patient age, sex, cyst type, and number of injections.

Results: Of the 75 treated patients, 31 (41.3%) showed total shrinkage, seven (9.3%) showed near‐total shrinkage (>90% of cyst volume), five (6.6%) showed marked shrinkage (>70% of cyst volume), and 17 (22.7%) showed partial shrinkage (<70% of cyst volume). No response was seen in 15 patients (20%). Despite repeated sclerotherapy, eight patients (10.7%) showed recurrences. Minor adverse effects of therapy included fever, localized pain, and odynophagia but these complications spontaneously disappeared within several days.

Conclusions: OK‐432 sclerotherapy is a safe and effective primary alternative to surgery in patients with benign neck cysts.
Antibody response to the 45 kDa Candida albicans antigen in an animal model and potential role of the antigen in adherence
Authors: Bujdáková Helena , Paulovičová Ema , Borecká-Melkusová Silvia , Gašperík Juraj , Kucharíková Soňa , Kolecka Anna , Lell Claudia , Jensen Dorthe B. , Würzner Reinhard , Chorvát Dušan , Pichová Iva
Published: November 2008

The Candida antigen CR3-RP (complement receptor 3-related protein) is supposed to be a ‘mimicry’ protein because of its ability to bind antibody directed against the α subunit of the mammalian CR3 (CD11b/CD18). This study aimed to (i) investigate the specific humoral isotypic response to immunization with CR3-RP in vivo in a rabbit animal model, and (ii) determine the role of CR3-RP in the adherence of Candida albicans in vitro using the model systems of buccal epithelial cells (BECs) and biofilm formation. The synthetic C. albicans peptide DINGGGATLPQ corresponding to 11 amino-acids of the CR3-RP sequence DINGGGATLPQALXQITGVIT, determined by N-terminal sequencing, was used for immunization of rabbits to obtain polyclonal anti-CR3-PR serum and for subsequent characterization of the humoral isotypic response of rabbits. A significant increase of IgG, IgA and IgM anti-CR3-RP specific antibodies was observed after the third (P<0.01) and the fourth (P<0.001) immunization doses. The elevation of IgA levels suggested peptide immunomodulation of the IgA1 subclass, presumably in coincidence with Candida epithelial adherence. Blocking CR3-RP with polyclonal anti-CR3-RP serum reduced the ability of Candida to adhere to BECs, in comparison with the control, by up to 35 % (P<0.001), and reduced biofilm formation by 28 % (P<0.001), including changes in biofilm thickness and integrity detected by confocal laser scanning microscopy. These properties of CR3-RP suggest that it has potential for future vaccine development.
Differentially expressed genes in Mycobacterium tuberculosis H37Rv under mild acidic and hypoxic conditions
Authors: Kim Su-Young , Lee Byung-Soo , Shin Sung Jae , Kim Hwa-Jung , Park Jeong-Kyu
Published: November 2008

The survival mechanism of dormant tubercle bacilli is unknown; however, accumulating evidence indicates that Mycobacterium tuberculosis can survive and persist in hypoxic and mildly acidic microenvironments. Such conditions are found in the acidic vacuoles of macrophages, which M. tuberculosis is known to target. We used DECAL (differential expression using customized amplification library) to identify the genes expressed under acidic and hypoxic conditions, following the cultivation of M. tuberculosis H37Rv at an acidic pH and/or under hypoxic or anoxic conditions in vitro. Of 960 clones analysed, 144 genes, consisting of 71 induced and 8 repressed genes, were identified by sequencing and divided into functional categories to characterize their cellular roles. In general, the genes induced under acidic and hypoxic conditions were involved in the biosynthesis of secondary metabolites (e.g. pks4), lipid metabolism, energy production (e.g. pckA) and cell wall biogenesis (e.g. Rv0696 and plcB). The combination of genes identified may explain the energy processing and energy storage of M. tuberculosis during latent infection. These findings not only enhance our understanding of the mechanism of dormancy, but they also may be useful in the design of therapeutic tools and vaccines for latent tuberculosis.
Bacterial DNA and its consequences in patients with cirrhosis and culture-negative, non-neutrocytic ascites
Authors: El-Naggar Mohammed Mahmoud , Khalil El-Sayed Abdul-Maksoud , El-Daker Medhat Abdul Massih , Salama Mona Fouda
Published: November 2008

The detection of bacterial DNA in serum and ascitic fluid (AF) from patients with liver cirrhosis and ascites is interpreted as molecular evidence of intestinal bacterial translocation (BT) and considered sufficient to activate the cellular immune response leading to greater cytokine synthesis. We studied 34 patients with liver cirrhosis and culture-negative, non-neutrocytic ascites [22 patients without bacterial DNA (group I) and 12 patients with bacterial DNA (group II)]. History and clinical examination were done with the following investigations at first admission and followed up for 24 weeks: serum and AF tumour necrosis factor-alpha (TNF-α), AF polymorphonuclear leukocytes, AF cultivation and detection of blood and AF bacterial DNA. Serum and AF TNF-α were significantly higher in patients with bacterial DNA compared to those without bacterial DNA at first admission [54.5±22.56 vs 35.2±17.97 pg ml−1 (P=0.02) and 123.2±49.32 vs 82.6±29.58 pg ml−1 (P <0.005), respectively]. These changes became highly significant at the end of follow-up of both groups [119.3±27.19 vs 40.2±16.08 pg ml−1 (P <0.001) and 518.8±91.11 vs 97.6±17.81 pg ml−1 (P <0.001), respectively]. In group II, there was a significant increase in serum and AF TNF-α at the end of follow-up compared to at first admission (P <0.001). The relative risk of death, hepatorenal syndrome (HRS) and spontaneous bacterial peritonitis (SBP) was higher in patients with bacterial DNA compared to those without bacterial DNA. We conclude that cirrhotic patients with culture-negative, non-neutrocytic ascites and bacterial DNA have a significantly higher level of serum and AF TNF-α and higher risk of HRS, SBP and mortality compared to those without bacterial DNA, suggesting that bacterial DNA and TNF-α are implicated in these complications of liver cirrhosis.
Increasing carbapenem resistance due to the clonal dissemination of oxacillinase (OXA-23 and OXA-58)-producing Acinetobacter baumannii: report from the Turkish SENTRY Program sites
Authors: Gur Deniz , Korten Volken , Unal Serhat , Deshpande Lalitagauri M. , Castanheira Mariana
Published: November 2008

A significant increase in carbapenem-resistance rates among Acinetobacter baumannii isolates collected in two Turkish medical centres was detected in the 2000–2006 period (20–60 %) by the SENTRY Antimicrobial Surveillance Program. Carbapenem-resistant strains from 2006 were evaluated for the presence of encoding genes and epidemic clonality. OXA-58-like and OXA-23-like carbapenemase-producing strains were detected in both medical institutions. Seventeen out of 18 strains from Ankara were positive for bla
OXA-58 primers and belonged to the same clone, whilst 26 isolates (25 from Istanbul and one from Ankara) harboured bla
OXA-23-like genes and showed identical or similar PFGE patterns. Isolates producing OXA-23-like carbapenemases were more resistant than OXA-58-like carbapenemase producers to non-carbapenem antimicrobial agents. Carbapenem resistance in these institutions was observed to be largely driven by the dissemination of clones producing OXA-type carbapenemases.
Antimicrobial susceptibility testing of Bordetella pertussis in Taiwan prompted by a case of pertussis in a paediatric patient
Authors: Yao Shu-Man , Liaw Gwo-Jen , Chen Ying-Yan , Yen Meng-Hsiu , Chen Ya-Hui , Mu Jung-Jung , Chiang Chuen-Sheue
Published: November 2008

In Taiwan, pertussis is a notifiable disease with a low incidence in recent years, and antimicrobial susceptibility testing for the causative agent, Bordetella pertussis, has not been reported to date. In May 2007, the Centers for Disease Control, Taiwan, was informed of a 1-month-old pertussis patient who did not respond to erythromycin treatment. In this study, we report the result of antimicrobial susceptibility testing performed for the suspected erythromycin-resistant isolate, as well as for an additional 27 B. pertussis clinical isolates that represented almost all epidemiologically unrelated isolates obtained throughout Taiwan between 2003 and 2007. All isolates were fully susceptible to azithromycin, erythromycin, clarithromycin and trimethoprim/sulfamethoxazole (MIC ≤0.047 μg ml−1). This result demonstrates the general susceptibility of B. pertussis to antimicrobial agents in vitro in Taiwan.
Helicobacter pylori virulence and the diversity of gastric cancer in Asia
Authors: Nguyen Lam Tung , Uchida Tomohisa , Murakami Kazunari , Fujioka Toshio , Moriyama Masatsugu
Published: November 2008

Infection with cagPAI positive strains of Helicobacter pylori is recognized as being associated with an increased risk of gastric cancer. This article reviews the current knowledge on the structures and pathological functions of cagPAI and the CagA protein, focusing especially on the molecular mechanism through which CagA may be involved in gastric carcinogenesis. The possible link between the geographical distribution of cagPAI and cagA variations and gastric cancer diversity in Asia is also discussed.
Polyhexamethylene guanidine hydrochloride-based disinfectant: a novel tool to fight meticillin-resistant Staphylococcus aureus and nosocomial infections
Authors: Oulé Mathias K. , Azinwi Richard , Bernier Anne-Marie , Kablan Tano , Maupertuis Anne-Marie , Mauler Stephanie , Nevry Rose K. , Dembélé Korami , Forbes Lorraine , Diop Lamine
Published: November 2008

Polyhexamethylene guanidine hydrochloride (PHMGH), an antimicrobial biocide of the guanidine family, was tested for efficacy against quality-control strains of Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella choleraesuis, meticillin-resistant S. aureus (MRSA) and Escherichia coli. Bactericidal activity against S. aureus, P. aeruginosa and Salmonella choleraesuis was determined using the official methods of analysis of the Association of Official Analytical Chemists, with modifications as recommended by the Canadian General Standards Board. For MRSA and E. coli, the MIC and minimal bactericidal concentration were determined using the broth dilution technique. The experiments were carried out at 20 °C under a range of conditions including varying PHMGH concentration (0.001–0.1 %), contact time (0.5–10 min) and water type (distilled, tap and hard water). The phenol coefficient values determined with S. aureus, Salmonella choleraesuis and P. aeruginosa were 7.5, 6.1 and 5, respectively. No matter what type of water was used to make the dilutions, PHMGH killed MRSA and E. coli at concentrations as low as 0.04 and 0.005 % (w/v), respectively, within 1.5 min. The mode of action of PHMGH was elucidated by transmission electron microscopy: the cell envelope was broken, resulting in cell content leakage into the medium. The ultimate aim of this study was to show that PHMGH can be used as an odourless, colourless, non-corrosive and harmless disinfectant for hospital and household facilities.
Simultaneous identification of molecular and mating types within the Cryptococcus species complex by PCR-RFLP analysis
Authors: Feng Xiaobo , Yao Zhirong , Ren Daming , Liao Wanqing
Published: November 2008

The Cryptococcus species complex consists of two species, Cryptococcus neoformans and Cryptococcus gattii, which cause systemic infections in both immunocompromised and immunocompetent patients. Both species have a bipolar mating system, with mating type (MAT) α being predominant in clinical and environmental isolates. The strains of the Cryptococcus species complex have been divided into eight major molecular types, which show differences in epidemiology, biology and pathogenicity. In this study, two PCR-RFLP analyses, based on the CAP1 and GEF1 genes, which are both located at the MAT locus, were developed for simultaneous identification of the molecular and mating types of isolates of the Cryptococcus species complex. The molecular and mating types of all 144 cryptococcal isolates, including rare subtypes, were successfully determined by both PCR-RFLP approaches. Pattern analysis of the AD hybrids revealed that the serotype A MAT
a allele in strains of AaDα derived from genotype VNB, whereas the serotype A MATα allele among strains of AαDa and AαDα derived from molecular type VNI.
Detection of Mycoplasma pneumoniae in adult community-acquired pneumonia by PCR and serology
Authors: Martínez María A. , Ruiz Mauricio , Zunino Enna , Luchsinger Vivian , Avendaño Luis F.
Published: November 2008

Diagnosis of pneumonia caused by Mycoplasma pneumoniae in adults is hampered by a lack of rapid and standardized tests for detection. This prospective study was conducted to compare the diagnostic values of an indirect immunofluorescence assay and a 16S rRNA gene PCR for the diagnosis of M. pneumoniae pneumonia in adults. From February 2005 to January 2008, 357 patients (53.8 % males, median age 63 years, range 18–94) admitted for community-acquired pneumonia (CAP) to two hospitals in Santiago, Chile, were enrolled in the study. Thirty-two patients (9.0 %) met the criteria of current or recent M. pneumoniae infection, and laboratory diagnosis was definitive in 26 cases (81.2 %) and presumptive in six cases (18.8 %). Among the 32 M. pneumoniae infections, the PCR assay was positive in 23 (71.9 %) and the serology in 27 (84.4 %) of the cases. IgM was positive in acute-phase serum specimens in 13 cases (40.6 %) of M. pneumoniae infections. Using serology as the gold standard, the sensitivity, specificity, and positive and negative predictive values of the PCR were 66.7, 98.5, 78.3 and 97.3 %, respectively, whereas the global agreement of the methods was 343/357 (96.1 %). The frequency of M. pneumoniae CAP cases declined significantly during the second year of study, suggesting the end of an epidemic period. In conclusion, although good global agreement was found between PCR and serology, the lower sensitivity of the PCR leads us to recommend the use of both procedures in parallel to confirm M. pneumoniae in CAP in adults.
Characteristics of a pandemic clone of O3 : K6 and O4 : K68 Vibrio parahaemolyticus isolated in Beira, Mozambique
Authors: Ansaruzzaman M. , Chowdhury Ashrafuzzaman , Bhuiyan Nurul A. , Sultana Marzia , Safa Ashrafus , Lucas Marcelino , von Seidlein Lorenz , Barreto Avertino , Chaignat Claire-Lise , Sack David A. , Clemens John D. , Nair G. Balakrish , Choi Seon Young , Jeon Yoon Seong , Lee Je Hee , Lee Hye Ri , Chun Jongsik , Kim Dong Wook
Published: November 2008

The genetic characteristics of Vibrio parahaemolyticus strains isolated in 2004 and 2005 in Mozambique were assessed in this study to determine whether the pandemic clone of V. parahaemolyticus O3 : K6 and O4 : K68 serotypes has spread to Mozambique. Fifty-eight V. parahaemolyticus strains isolated from hospitalized diarrhoea patients in Beira, Mozambique, were serotyped for O : K antigens and genotyped for toxR, tdh and trh genes. A group-specific PCR, a PCR that detects the presence of ORF8 of the filamentous phage f237, arbitrarily primed PCR, PFGE and multilocus sequence typing were performed to determine the pandemic status of the strains and their ancestry. All strains of serovars O3 : K6 (n=38) and O4 : K68 (n=4) were identified as a pandemic clonal group by these analyses. These strains are closely related to the pandemic reference strains of O3 : K6 and O4 : K68, which emerged in Asia in 1996 and were later found globally. The pandemic serotypes O3 : K6 and O4 : K68 including reference strains grouped into a single cluster indicating emergence from a common ancestor. The O3 : K58 (n=8), O4 : K13 (n=6), O3 : KUT (n=1) and O8 : K41 (n=1) strains showed unique characteristics different from the pandemic clone.
Transcriptome analyses and biofilm-forming characteristics of a clonal Pseudomonas aeruginosa from the cystic fibrosis lung
Authors: Manos Jim , Arthur Jonathan , Rose Barbara , Tingpej Pholawat , Fung Carina , Curtis Michelle , Webb Jeremy S. , Hu Honghua , Kjelleberg Staffan , Gorrell Mark D. , Bye Peter , Harbour Colin
Published: November 2008

TransmissiblePseudomonas aeruginosaclones potentially pose a serious threat to cystic fibrosis (CF) patients. The AES-1 clone has been found to infect up to 40 % of patients in five CF centres in eastern Australia. Studies were carried out on clonal and non-clonal (NC) isolates from chronically infected CF patients, and the reference strain PAO1, to gain insight into the properties of AES-1. The transcriptomes of AES-1 and NC isolates, and of PAO1, grown planktonically and as a 72 h biofilm were compared using PAO1 microarrays. Microarray data were validated using real-time PCR. Overall, most differentially expressed genes were downregulated. AES-1 differentially expressed bacteriophage genes, novel motility genes, and virulence and quorum-sensing-related genes, compared with both PAO1 and NC. AES-1 but not NC biofilms significantly downregulated aerobic respiration genes compared with planktonic growth, suggesting enhanced anaerobic/microaerophilic growth by AES-1. Biofilm measurement showed that AES-1 formed significantly larger and thicker biofilms than NC or PAO1 isolates. This may be related to expression of the gene PA0729, encoding a biofilm-enhancing bacteriophage, identified by PCR in all AES-1 but few NC isolates (n=42). Links with the Liverpool epidemic strain included the presence of PA0729 and the absence of the bacteriophage gene cluster PA0632–PA0639. No common markers were found with the Manchester strain. No particular differentially expressed gene in AES-1 could definitively be ascribed a role in its infectivity, thus increasing the likelihood that AES-1 infectivity is multi-factorial and possibly involves novel genes. This study extends our understanding of the transcriptomic and genetic differences between clonal and NC strains ofP. aeruginosafrom CF lung.