bluuebunny/crossref_metadata_2025 huggingface dataset:
Meningitis Due to Hematogenous Dissemination of Community-Associated Methicillin-Resistant Staphylococcus aureus (MRSA) in a Patient With AIDS
Authors: Sayana Shilpa , Khanlou Homayoon
Published: October 2008

Meningitis due to methicillin-resistant Staphylococcus aureus is a rare clinical presentation but has been well documented in postneurosurgical patients. To our knowledge, no case of methicillin-resistant Staphylococcus aureus meningitis has been previously reported in a nonneurosurgical patient with AIDS. In this case report we describe a person with AIDS who had no history of a neurosurgical procedure, shunt devices, head trauma, or recent hospitalization that presented with methicillin-resistant Staphylococcus aureus meningitis. The infection was successfully treated. Methicillin-resistant Staphylococcus aureusshould be considered in the differential of meningitis in people with AIDS.
A Computer-Tailored Intervention to Promote Informed Decision Making for Prostate Cancer Screening Among African American Men
Authors: Allen Jennifer D. , Mohllajee Anshu P. , Shelton Rachel C. , Drake Bettina F. , Mars Dana R.
Published: October 2008

African American men experience a disproportionate burden of prostate cancer (CaP) morbidity and mortality. National screening guidelines advise men to make individualized screening decisions through a process termed informed decision making (IDM). In this pilot study, a computer-tailored decision-aid designed to promote IDM was evaluated using a pre-/posttest design. African American men aged 40 years and older were recruited from a variety of community settings ( n = 108). At pretest, 43% of men reported having made a screening decision; at posttest 47% reported this to be the case ( p = .39). Significant improvements were observed between pre- and posttest on scores of knowledge, decision self-efficacy, and decisional conflict. Men were also more likely to want an active role in decision making after using the tool. These results suggest that use of a computer-tailored decision aid is a promising strategy to promote IDM for CaP screening among African American men.
Congenital Bilateral Pseudarthrosis of the Index Metacarpal Bones
Authors: TAHERI H. , JAFARI D. , MAZHAR F. NAJD
Published: October 2008

Congenital pseudarthrosis is very rare in upper extremity, and has only previously been reported in the forearm. A case of bilateral congenital pseudarthrosis of the index metacarpal bones is described.
The Non-Dissociative Clunking Wrist: A Personal View
Authors: GARCIA-ELIAS M.
Published: October 2008

Clunking of the wrist is often the result of a combined radiocarpal and midcarpal ligament insufficiency, coupled with inadequate neuromuscular coordination. When symptomatic, these wrists may benefit from splinting, isometric exercising of specific muscles and advice on activity modification. Failing this, different surgical strategies have been proposed, depending on the location of dysfunction. When the clunking derives from an isolated injury of one joint, reconstruction of its inadequate ligaments may be an effective solution. However, soft tissue procedures tend to fail when clunking results from multilevel instability. In these cases, partial carpal arthrodesis is an alternative. Although effective in eliminating the clunking, midcarpal fusion is associated with alteration of the so-called “dart-throwing” motion, the most common rotation in daily activities, and hence is not recommended. Radiolunate fusion, by contrast, appears to be a less morbid alternative, with the benefit of eliminating the painful clunking while preserving a good range of dart-throwing motion.
Phalangeal Neck Fractures with Concurrent Vascular Injury
Authors: AL-QATTAN M. M.
Published: October 2008

The outcome in 16 consecutive paediatric cases of phalangeal neck fractures with concurrent vascular injury was investigated. The study group had a mean age of 5 (range 3–11) years. At final follow-up, the outcome was assessed according to Al-Qattan’s grading system. The study population was divided into three groups. In group A ( n = 3), there was circumferential skin laceration with disruption of both digital arteries and all three patients ended up with an amputation. In group B ( n = 11), there was skin laceration on one side of the digit with one disrupted digital artery, and the outcome following surgery was considered good in six, fair in four and poor in the remaining patient. Group C ( n = 2) presented with “congested” digits and conservative management resulted in one good and one poor result. Reasons for failure to obtain a single excellent result are discussed. Phalangeal neck fractures with concurrent vascular injury should raise a “red flag” and outcomes may be limited, despite management in a specialist hand surgery facility.
Proximal Row Carpectomy With or Without Postoperative Immobilisation
Authors: JACOBS R. , DEGREEF I. , DE SMET L.
Published: October 2008

Previously published reports have shown good results after proximal row carpectomy in all cases that had a postoperative immobilisation period from 1 to 4 weeks. Immobilisation is thought to be necessary because of the risk of postoperative subluxation of the carpus and for pain relief. There is, however, no evidence of its value. The results in 13 patients who underwent proximal row carpectomy without postoperative immobilisation were compared with those in 25 patients who underwent proximal row carpectomy with postoperative immobilisation for 4 weeks. After a mean follow-up period of 27 months, no significant differences were found for pain, range of motion or return to work between the two groups. We conclude that postoperative immobilisation is not necessary after proximal row carpectomy.
The Clinical Significance of Malunion of Fractures of the Neck and Shaft of the Little Finger Metacarpal
Authors: WESTBROOK A. P. , DAVIS T. R. C. , ARMSTRONG D. , BURKE F. D.
Published: October 2008

The outcomes of 218 little finger metacarpal shaft and neck fractures that had been treated non-operatively, with no attempt at fracture reduction, were compared with those of 44 that had been treated operatively with fracture reduction and fixation (plates or K-wires). Outcome measures included the grip strength of the little finger and the DASH score. Fracture malunion was assessed by clinical measurement of little finger ray shortening and measurement of palmar angulation on the initial radiographs. The severity of palmar angular deformity did not affect the outcome of the 105 metacarpal neck or 113 metacarpal shaft fractures that had been treated non-operatively. There were no differences between the outcomes of the 18 metacarpal neck fractures treated operatively and the 105 treated non-operatively. The DASH score ( P = 0.001) and aesthetic outcome ( P = 0.013) were significantly better for the 113 metacarpal shaft fractures treated non-operatively than for the 26 treated operatively.
Analysis of the Mechanism of Fracture of Silicone Metacarpophalangeal Prostheses
Authors: JOYCE T. J.
Published: October 2008

Eleven fractured Sutter metacarpophalangeal prostheses were obtained from the hands of three patients. All of the implants had fractured at the junction of the distal stem and the hinge. After visual examination, the fracture faces were prepared and viewed using a scanning electron microscope. These images indicated that fracture was initiated by abrasion on the dorsal aspect of the distal stem of the prostheses, close to the hinge. Crack propagation was shown to be due to a fatigue process. Once a crack started, its direction of travel could be followed, using topographical features common to engineering fracture analyses. Propagation was from radial to ulnar and from dorsal to palmar.
Changes in Speed of Information Processing in the Brain Following Tendon Repair
Authors: STENEKES M. W. , VAN DER SLUIS C. K. , NICOLAI J. -P. A. , GEERTZEN J. H. B. , MULDER TH.
Published: October 2008

The objective of this study was to measure the “preparation time” that is the speed of information processing in the brain, and discuss the relevance of this parameter in the restoration of hand function following flexor tendon repair. The preparation time of 48 healthy adult participants was measured twice at a 6-week interval and compared with that of 12 patients after flexor tendon repair. There was no difference between the left and right hands of the healthy participants. The correlation between repeated measurements was high, although healthy participants performed 2.6% faster 6 weeks after the first measurement. After 6 weeks of immobilisation, patients showed a significant deterioration with respect to the speed of information processing by the brain on both the injured and uninjured sides compared with healthy participants, who had improved between the first and the second measurements. The results indicate that a period of lack of normal use of the hand leads to a change in cerebral control of hand movements.
Ageing Does Not Affect Ulnar Variance: An Investigation in Taiwan
Authors: CHEN W. -S. , WANG J. -W.
Published: October 2008

This paper presents a longitudinal study of the effect of ageing on ulnar variance. Between 1976 and 1985, ulnar variance in 1000 normal adult subjects was measured using the Palmer method. In 1995 to 2002, 17 to 22 years later, the ulnar variance was measured again in 864 of them. They were stratified into three age groups: Group I consisted of 351 subjects of young age (20–39 year-old), Group II of 318 subjects of middle age (40–59 year-old) and group III of 195 subjects of old age (60 year-old or older). The means of the initial and the final ulnar variance of the whole series and the three groups were compared by the paired Student’s t-test. There were no significant differences between the initial and final ulnar variances in all three age groups and in the whole series. In normal subjects without diseases or injuries affecting the wrist, ageing does not affect the ulnar variance.
Reanimation of Thumb Extension after Upper Extremity Degloving Injury Treated with Integra®
Authors: KATRANA F. , KOSTOPOULOS E. , DELIA G. , LUNEL G. GOUDET , CASOLI V.
Published: October 2008

A case of severe degloving injury to the left hand with complete destruction of the extensor apparatus of the thumb and exposure of the IP joint is presented. The damaged area was resurfaced with the use of the Integra® template and the abductor pollicis longus tendon, lengthened with a tendon graft provided by the extensor indicis, and used to restore thumb extension. The transfer was performed through a prefabricated sheath under the Integra® resurfaced area in a two-staged procedure. The final result was functional and aesthetically satisfying.
Effects of strain on grain boundary characteristics and their correlation to mechanical properties in low carbon steel processed by warm multipass calibre rolling
Authors: Narayana Murty S. V. S. , Torizuka S. , Nagai K. , Kitai T. , Kogo Y.
Published: October 2008

The effect of strain on the grain boundary characteristics and their correlation to mechanical properties is studied in detail in low carbon steel processed by warm multipass calibre rolling. It was noted that strength properties are controlled by the total grain boundary length but not grain boundary character or their fraction. On the other hand, impact properties are controlled by the length fraction of high angle grain boundaries. Finally, it was noted that low angle boundaries are found to be helpful in improving the strength whereas they are harmful for impact properties.
Study on microstructures and grain boundary penetration behaviours in contact reactive brazing joints of 6063 Al alloy
Authors: Wu M. F. , Yu C. , Pu J.
Published: October 2008

Contact reactive brazing on 6063 Al alloy has been conducted by using Cu foil or Cu foil–Mg powder–Cu foil multilayer as interlayer. The microstructures of the joints and grain boundary penetration phenomenon were analysed and discussed primarily. The results showed that the microstructure of the reaction zone consisted of α-Al solid solution and CuAl2 compound as monolayer Cu foil was used, and meantime, obvious grain boundary penetration phenomenon at the reaction interface was found. However, the reaction zone of the joint bonded with Cu foil–Mg powder–Cu foil was composed of Al(Mg, Cu) solid solution, CuAl2 intermetallic compound, Cu–Al–Mg ternary intermetallic compound and Al2MgO4. It was also found that the grain boundary penetration phenomenon was delayed as Mg powder was added into the interlayer.
Modelling and simulation of equiaxed dendritic structures permeability for Pb–Sn alloys
Authors: Mirbagheri S. M. H. , Khajeh E.
Published: October 2008

In this investigation, the permeability of interdendritic liquid flow through the equiaxial mushy zone has been modelled for Pb–Sn alloys based on experimental measurements. In the present work by solving Navier–Stokes equation, the flow pattern around the equiaxed dendrite has been obtained and then permeability has been determined by applying Darcy's law. Numerical determined values of permeabilities have been analysed by the use of Statistical Package for the Social Sciences (SPSS) statistical software. Then an experimental method has been used to measure the permeability for flow through equiaxial mushy zone of Pb–Sn alloys. Results show that increasing the solid fraction and perturbation decreases the permeability, but unlike the solid fraction, perturbation has less effect on permeability. It seems that the empirical relationship presented in this article could be used to estimate permeability in the mushy Pb–Sn alloys.
Development of porous 316L stainless steel with controllable microcellular features using selective laser melting
Authors: Shen Y. F. , Gu D. D. , Wu P.
Published: October 2008

The regularly shaped parallel pore gas armed (GASAR) stainless steel porous material with a homogeneous size distribution of unusually micrometer scaled pores (2 μm in average) was successfully prepared using selective laser melting process, by adding 0·10 wt-% gas generating materials in the form of H3BO3 and KBF4. The adjustment of pore morphology, pore direction, and porosity was realised by changing material combinations (such as the content of additive materials) and processing conditions (such as the scan speed of laser beam).
Effect of Sc addition on microstructure and mechanical properties of Al–Cu–Mg–Ag–Zr alloy
Authors: Xiao D. H. , Song M. , Huang B. Y. , Yi J. H. , He Y. H. , Li Y. M.
Published: October 2008

Al–Cu–Mg–Ag–Zr alloys containing 0, 0·1, 0·3 and 0·5 mass%Sc were prepared by ingot metallurgy and thermomechanical treatment. The effect of Sc addition on the precipitation and microstructure of the alloys has been investigated by using mechanical testing, optical microscopy, scanning electron microscopy and transmission electron microscopy. It has been shown that trace Sc element refines the grains of the casting alloys and the average grain size decreases from 85 to 30 μm. Increasing Sc content from 0·1 to 0·3% accelerates the aging hardening process, increases the maximum hardness and the yield strength of the extruded alloys from room temperature to 300°C. The high strength of the alloys with Sc is attributed to the high density and high thermal stability of fine Ω precipitates, and nanosized Al3(Sc,Zr) and AlCu(Zr,Sc) particles.
Coupled heat and fluid flow model and experimental verification of aluminium plate die casting
Authors: Taha M. A. , El-Mahallawy N. A. , El-Sabbagh A. M.
Published: October 2008

The present work aims to forecast mould filling, void shape, location and size as well as columnar to equiaxed transition (CET) in commercial pure aluminium casting. A model coupling the momentum equations of the fluid flow and heat transfer equations is presented, in which metallostatic pressure, air gap and oxide layer are considered. Different casting parameters were investigated such as casting configuration by varying the plate thickness from 5 to 20 mm, melt superheat from 40 to 120°C, mould preheat up to 200°C and different pouring heads ranging from 0·3 to 0·6 m. Regarding the microstructure and void formation, the approach based on the Niyama criterion, was considered. The experimental verification of the model was achieved by gravity die casting in the form of a rectangular cavity. Voids inside aluminium plate were investigated by X-ray imaging. Microstructure and CET was investigated microscopically. The supposed model proves its validity for mould filling and in detecting the void features and CET.
Effects of Mg doping on sol–gel derived nanocrystalline hydroxyapatite thin films
Authors: Köseoğlu N. C. , Büyükaksoy A. , Aslan M. H. , Oral A. Y.
Published: October 2008

Both pure and Mg doped thin films were fabricated by sol–gel dip coating. The films were sintered either at 800 or 1000°C. The average grain size of the films was significantly affected by Mg substitution in the hydroxyapatite (HA) structure and change in the sintering temperature. The grains were considerably larger in the films sintered at higher temperatures. In addition, Mg doped films contained significantly larger grains compared to undoped HA films. Mg doping also caused rodlike grains at 800°C, and led to whitlockite ( β-TCP) formation at 1000°C. The ratio of the existing phases was estimated as β-TCP/HA=27 : 73. All the films had rough surfaces with high porosity. It was also observed that undoped films had higher surface roughness than Mg doped ones.
miR-34a as part of the resistance network in chronic lymphocytic leukemia
Authors: Zenz Thorsten , Mohr Julia , Eldering Eric , Kater Arnon P. , Bühler Andreas , Kienle Dirk , Winkler Dirk , Dürig Jan , van Oers Marinus H. J. , Mertens Daniel , Döhner Hartmut , Stilgenbauer Stephan
Published: October 2008

17p (TP53) deletion identifies patients with chronic lymphocytic leukemia (CLL) who are resistant to chemotherapy. The members of the miR-34 family have been discovered to be direct p53 targets and mediate some of the p53-dependent effects. We studied miR-34a and miR-34b/c expression in a large cohort to define their potential role in refractory CLL. While no expression of miR-34b/c could be detected, we found variable expression levels of miR-34a. miR-34a levels were up-regulated after DNA damage in the presence of functional p53, but not in cases with 17p deletion (P < .001). We found a strong correlation of low miR-34a levels with impaired DNA damage response, TP53 mutations (without 17p deletion), and fludarabine-refractory disease (also in the absence of 17p deletion). Up-regulation of miR-34a after irradiation was associated with induction of Bax and p21, but not Puma. CLL cells with reduced miR-34a expression showed increased viability after DNA damage independently of 17p status. Therefore, low expression of miR-34a in CLL is associated with p53 inactivation but also chemotherapy-refractory disease, impaired DNA damage response, and apoptosis resistance irrespective of 17p deletion/TP53 mutation. The elucidation of mechanisms underlying miR-34a regulation and overcoming its role in chemotherapy resistance warrant further study.
The UPS: a promising target for breast cancer treatment
Authors: Sato Ko , Rajendra Eeson , Ohta Tomohiko
Published: October 2008

During the past decade, progress in endocrine therapy and the use of trastuzumab has significantly contributed to the decline in breast cancer mortality for hormone receptor-positive and ERBB2 (HER2)-positive cases, respectively. As a result of these advances, a breast cancer cluster with poor prognosis that is negative for the estrogen receptor (ESR1), the progesterone receptor (PRGR) and ERBB2 (triple negative) has come to the forefront of medical therapeutic attention. DNA microarray analyses have revealed that this cluster is phenotypically most like the basal-like breast cancer that is caused by deficiencies in the BRCA1 pathways. To gain further improvements in breast cancer survival, new types of drugs might be required, and small molecules targeting the ubiquitin proteasome system have moved into the spotlight. The success of bortezomib in the treatment of multiple myeloma has sent encouraging signals that proteasome inhibitors could be used to treat other types of cancers. In addition, ubiquitin E3s involved in ESR1, ERBB2 or BRCA1 pathways could be ideal targets for therapeutic intervention. This review summarizes the ubiquitin proteasome pathways related to these proteins and discusses the possibility of new drugs for the treatment of breast cancers.

Publication history

Republished from Current BioData's Targeted Proteins database (TPdb;http://www.targetedproteinsdb.com).
Deubiquitylating enzymes and disease
Authors: Singhal Shweta , Taylor Matthew C , Baker Rohan T
Published: October 2008

Deubiquitylating enzymes (DUBs) can hydrolyze a peptide, amide, ester or thiolester bond at the C-terminus of UBIQ (ubiquitin), including the post-translationally formed branched peptide bonds in mono- or multi-ubiquitylated conjugates. DUBs thus have the potential to regulate any UBIQ-mediated cellular process, the two best characterized being proteolysis and protein trafficking. Mammals contain some 80–90 DUBs in five different subfamilies, only a handful of which have been characterized with respect to the proteins that they interact with and deubiquitylate. Several other DUBs have been implicated in various disease processes in which they are changed by mutation, have altered expression levels, and/or form part of regulatory complexes. Specific examples of DUB involvement in various diseases are presented. While no specific drugs targeting DUBs have yet been described, sufficient functional and structural information has accumulated in some cases to allow their rapid development.

Publication history

Republished from Current BioData's Targeted Proteins database (TPdb; http://www.targetedproteinsdb.com).
A machine vision system for automated non-invasive assessment of cell viability via dark field microscopy, wavelet feature selection and classification
Authors: Wei Ning , Flaschel Erwin , Friehs Karl , Nattkemper Tim Wilhelm
Published: October 2008

Background

Cell viability is one of the basic properties indicating the physiological state of the cell, thus, it has long been one of the major considerations in biotechnological applications. Conventional methods for extracting information about cell viability usually need reagents to be applied on the targeted cells. These reagent-based techniques are reliable and versatile, however, some of them might be invasive and even toxic to the target cells. In support of automated noninvasive assessment of cell viability, a machine vision system has been developed.

Results

This system is based on supervised learning technique. It learns from images of certain kinds of cell populations and trains some classifiers. These trained classifiers are then employed to evaluate the images of given cell populations obtained via dark field microscopy. Wavelet decomposition is performed on the cell images. Energy and entropy are computed for each wavelet subimage as features. A feature selection algorithm is implemented to achieve better performance. Correlation between the results from the machine vision system and commonly accepted gold standards becomes stronger if wavelet features are utilized. The best performance is achieved with a selected subset of wavelet features.

Conclusion

The machine vision system based on dark field microscopy in conjugation with supervised machine learning and wavelet feature selection automates the cell viability assessment, and yields comparable results to commonly accepted methods. Wavelet features are found to be suitable to describe the discriminative properties of the live and dead cells in viability classification. According to the analysis, live cells exhibit morphologically more details and are intracellularly more organized than dead ones, which display more homogeneous and diffuse gray values throughout the cells. Feature selection increases the system's performance. The reason lies in the fact that feature selection plays a role of excluding redundant or misleading information that may be contained in the raw data, and leads to better results.
Aggresomes do not represent a general cellular response to protein misfolding in mammalian cells
Authors: Beaudoin Simon , Goggin Kevin , Bissonnette Cyntia , Grenier Catherine , Roucou Xavier
Published: October 2008

Background

Aggresomes are juxtanuclear inclusion bodies that have been proposed to represent a general cellular response to misfolded proteins in mammalian cells. Yet, why aggresomes are not a pathological characteristic of protein misfolding diseases is unclear. Here, we investigate if a misfolded protein inevitably forms aggresomes in mammalian cells.

Results

We show that a cytoplasmic form of the prion protein may form aggresomes or dispersed aggregates in different cell lines. In contrast to aggresomes, the formation of dispersed aggregates is insensitive to histone deacetylase 6 inhibitors and does not result in cytoskeleton rearrangements. Modulation of expression levels or proteasome inhibitors does not alter the formation of dispersed aggregates.

Conclusion

Our results establish that aggresomes are not obligatory products of protein misfolding in vivo.
Empirical Bayes accomodation of batch-effects in microarray data using identical replicate reference samples: application to RNA expression profiling of blood from Duchenne muscular dystrophy patients
Authors: Walker Wynn L , Liao Isaac H , Gilbert Donald L , Wong Brenda , Pollard Katherine S , McCulloch Charles E , Lit Lisa , Sharp Frank R
Published: October 2008

Background

Non-biological experimental error routinely occurs in microarray data collected in different batches. It is often impossible to compare groups of samples from independent experiments because batch effects confound true gene expression differences. Existing methods can correct for batch effects only when samples from all biological groups are represented in every batch.

Results

In this report we describe a generalized empirical Bayes approach to correct for cross-experimental batch effects, allowing direct comparisons of gene expression between biological groups from independent experiments. The proposed experimental design uses identical reference samples in each batch in every experiment. These reference samples are from the same tissue as the experimental samples. This design with tissue matched reference samples allows a gene-by-gene correction to be performed using fewer arrays than currently available methods. We examine the effects of non-biological variation within a single experiment and between experiments.

Conclusion

Batch correction has a significant impact on which genes are identified as differentially regulated. Using this method, gene expression in the blood of patients with Duchenne Muscular Dystrophy is shown to differ for hundreds of genes when compared to controls. The numbers of specific genes differ depending upon whether between experiment and/or between batch corrections are performed.
PrimerSNP: a web tool for whole-genome selection of allele-specific and common primers of phylogenetically-related bacterial genomic sequences
Authors: Yao Jiqiang , Lin Hong , Van Deynze Allen , Doddapaneni Harshavardhan , Francis Martha , Lemos Eliana Gertrudes Macedo , Civerolo Edwin L
Published: October 2008

Background

The increasing number of genomic sequences of bacteria makes it possible to select unique SNPs of a particular strain/species at the whole genome level and thus design specific primers based on the SNPs. The high similarity of genomic sequences among phylogenetically-related bacteria requires the identification of the few loci in the genome that can serve as unique markers for strain differentiation. PrimerSNP attempts to identify reliable strain-specific markers, on which specific primers are designed for pathogen detection purpose.

Results

PrimerSNP is an online tool to design primers based on strain specific SNPs for multiple strains/species of microorganisms at the whole genome level. The allele-specific primers could distinguish query sequences of one strain from other homologous sequences by standard PCR reaction. Additionally, PrimerSNP provides a feature for designing common primers that can amplify all the homologous sequences of multiple strains/species of microorganisms. PrimerSNP is freely available at http://cropdisease.ars.usda.gov/~primer.

Conclusion

PrimerSNP is a high-throughput specific primer generation tool for the differentiation of phylogenetically-related strains/species. Experimental validation showed that this software had a successful prediction rate of 80.4 – 100% for strain specific primer design.
Role of protease activated receptor-2 in lymph node metastasis of uterine cervical cancers
Authors: Jahan Israt , Fujimoto Jiro , Alam Syed Mahfuzul , Sato Eriko , Tamaya Teruhiko
Published: October 2008

Background

Protease activated receptor-2 (PAR-2) has been implicated in cellular proliferation, invasion and metastasis in various tumors. Lymph node metastasis is an important patient prognostic factor for uterine cervical cancers. This prompted us to study the role of PAR-2 in lymph node metastasis of uterine cervical cancers.

Methods

Thirty patients underwent surgery for uterine cervical cancers. PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. Patient prognosis was analyzed with a 48-month survival rate.

Results

PAR-2 histoscores and mRNA levels significantly (P< 0.05) increased in 12 of 30 metastatic lymph node lesions from the corresponding primary tumor. The 48-month survival rate of the 12 patients with increased PAR-2 levels in metastatic lymph nodes was 42%, while the rate of the other 18 patients with no change in PAR-2 levels was 82%, regardless of histopathological type.

Conclusion

PAR-2 might work on lymph node metastasis of uterine cervical cancers, and is considered to be a novel prognostic indicator for uterine cervical cancers.
STAT3 can be activated through paracrine signaling in breast epithelial cells
Authors: Lieblein Jacqueline C , Ball Sarah , Hutzen Brian , Sasser A Kate , Lin Huey-Jen , Huang Tim HM , Hall Brett M , Lin Jiayuh
Published: October 2008

Background

Many cancers, including breast cancer, have been identified with increased levels of phosphorylated or the active form of Signal Transducers and Activators of Transcription 3 (STAT3) protein. However, whether the tumor microenvironment plays a role in this activation is still poorly understood.

Methods

Conditioned media, which contains soluble factors from MDA-MB-231 and MDA-MB-468 breast cancer cells and breast cancer associated fibroblasts, was added to MCF-10A breast epithelial and MDA-MB-453 breast cancer cells. The stimulation of phosphorylated STAT3 (p-STAT3) levels by conditioned media was assayed by Western blot in the presence or absence of neutralized IL-6 antibody, or a JAK/STAT3 inhibitor, JSI-124. The stimulation of cell proliferation in MCF-10A cells by conditioned media in the presence or absence of JSI-124 was subjected to MTT analysis. IL-6, IL-10, and VEGF levels were determined by ELISA analysis.

Results

Our results demonstrated that conditioned media from cell lines with constitutively active STAT3 are sufficient to induce p-STAT3 levels in various recipients that do not possess elevated p-STAT3 levels. This signaling occurs through the JAK/STAT3 pathway, leading to STAT3 phosphorylation as early as 30 minutes and is persistent for at least 24 hours. ELISA analysis confirmed a correlation between elevated levels of IL-6 production and p-STAT3. Neutralization of the IL-6 ligand or gp130 was sufficient to block increased levels of p-STAT3 (Y705) in treated cells. Furthermore, soluble factors within the MDA-MB-231 conditioned media were also sufficient to stimulate an increase in IL-6 production from MCF-10A cells.

Conclusion

These results demonstrate STAT3 phosphorylation in breast epithelial cells can be stimulated by paracrine signaling through soluble factors from both breast cancer cells and breast cancer associated fibroblasts with elevated STAT3 phosphorylation. The induction of STAT3 phosphorylation is through the IL-6/JAK pathway and appears to be associated with cell proliferation. Understanding how IL-6 and other soluble factors may lead to STAT3 activation via the tumor microenvironment will provide new therapeutic regimens for breast carcinomas and other cancers with elevated p-STAT3 levels.
Implementation of Home based management of malaria in children reduces the work load for peripheral health facilities in a rural district of Burkina Faso
Authors: Tiono Alfred B , Kaboré Youssouf , Traoré Abdoulaye , Convelbo Nathalie , Pagnoni Franco , Sirima Sodiomon B
Published: October 2008

Background

Home Management of Malaria (HMM) is one of the key strategies to reduce the burden of malaria for vulnerable population in endemic countries. It is based on the evidence that well-trained communities health workers can provide prompt and adequate care to patients close to their homes. The strategy has been shown to reduce malaria mortality and severe morbidity and has been adopted by the World Health Organization as a cornerstone of malaria control in Africa. However, the potential fall-out of this community-based strategy on the work burden at the peripheral health facilities level has never been investigated.

Methods

A two-arm interventional study was conducted in a rural health district of Burkina Faso. The HMM strategy has been implemented in seven community clinics catchment's area (intervention arm). For the other seven community clinics in the control arm, no HMM intervention was implemented. In each of the study arms, presumptive treatment was provided for episodes of fevers/malaria (defined operationally as malaria).

The study drug was artemether-lumefantrine, which was sold at a subsidized price by community health workers/Key opinion leaders at the community level and by the pharmacists at the health facility level.

The outcome measured was the proportion of malaria cases among all health facility attendance (all causes diseases) in both arms throughout the high transmission season.

Results

A total of 7,621 children were enrolled in the intervention arm and 7,605 in the control arm. During the study period, the proportions of malaria cases among all health facility attendance (all causes diseases) were 21.0%, (445/2,111, 95% CI [19.3%–22.7%]) and 70.7% (2,595/3,671, 95% CI 68.5%–71.5%), respectively in the intervention and control arms (p << 0.0001). The relative risk ratio for a fever/malaria episode to be treated at the HF level was 30% (0.30 < RR < 0.32).

The number of malaria episodes treated in the intervention arm was much higher than in the control arm (6,661 vs. 2,595), with malaria accounting for 87.4% of all disease episodes recorded in the intervention area and for 34.1% in the control area (P < 0.0001). Of all the malaria cases treated in the intervention arm, only 6.7% were treated at the health facility level.

Conclusion

These findings suggest that implementation of HMM, by reducing the workload in health facilities, might contributes to an overall increase of the performance of the peripheral health facilities.
Interaction of an atypical Plasmodium falciparum ETRAMP with human apolipoproteins
Authors: Vignali Marissa , McKinlay Anastasia , LaCount Douglas J , Chettier Rakesh , Bell Russell , Sahasrabudhe Sudhir , Hughes Robert E , Fields Stanley
Published: October 2008

Background

In order to establish a successful infection in the human host, the malaria parasite Plasmodium falciparum must establish interactions with a variety of human proteins on the surface of different cell types, as well as with proteins inside the host cells. To better understand this aspect of malaria pathogenesis, a study was conducted with the goal of identifying interactions between proteins of the parasite and those of its human host.

Methods

A modified yeast two-hybrid methodology that preferentially selects protein fragments that can be expressed in yeast was used to conduct high-throughput screens with P. falciparum protein fragments against human liver and cerebellum libraries. The resulting dataset was analyzed to exclude interactions that are not likely to occur in the human host during infection.

Results

An initial set of 2,200 interactions was curated to remove proteins that are unlikely to play a role in pathogenesis based on their annotation or localization, and proteins that behave promiscuously in the two-hybrid assay, resulting in a final dataset of 456 interactions. A cluster that implicates binding between P. falciparum PFE1590w/ETRAMP5, a putative parasitophorous vacuole membrane protein, and human apolipoproteins ApoA, ApoB and ApoE was selected for further analysis. Different isoforms of ApoE, which are associated with different outcomes of malaria infection, were shown to display differential interactions with PFE1590w.

Conclusion

A dataset of interactions between proteins of P. falciparum and those of its human host was generated. The preferential interaction of the P. falciparum PFE1590w protein with the human ApoE ε3 and ApoE ε4 isoforms, but not the ApoE ε2 isoform, supports the hypothesis that ApoE genotype affects risk of malaria infection. The dataset contains other interactions of potential relevance to disease that may identify possible vaccine candidates and drug targets.
Differences in genetic population structures of Plasmodium falciparum isolates from patients along Thai-Myanmar border with severe or uncomplicated malaria
Authors: Susomboon Pannapa , Iwagami Moritoshi , Tangpukdee Noppadon , Krusood Srivicha , Looareesuwan Sornchai , Kano Shigeyuki
Published: October 2008

Background

There have been many reports on the population genetic structures ofPlasmodium falciparumfrom different endemic regions, but few studies have examined the characteristics of isolates from patients with different clinical outcomes. The population genetic structures ofP. falciparumisolates from patients with either severe or uncomplicated malaria were examined.

Methods

Twelve microsatellite DNA loci fromP. falciparumwere used to assess the population genetic structures of 50 isolates (i.e., 25 isolates from patients with severe malaria and 25 from patients with uncomplicated malaria) collected in the Thai-Myanmar border area between 2002 and 2005.

Results

Genetic diversity and effective population sizes were greater in the uncomplicated malaria group than in the severe malaria group. Evidence of genetic bottlenecks was not observed in either group. Strong linkage disequilibrium was observed in the uncomplicated malaria group. The groups demonstrated significant genetic differentiation (P< 0.05), and allele frequencies for 3 of the 12 microsatellite loci differed significantly between the two groups.

Conclusion

These findings suggest that the genetic structure ofP. falciparumpopulations in patients with severe malaria differs from that in patients with uncomplicated malaria. The microsatellite loci used in this study were presumably unrelated to antigenic features of the parasites, but, these findings suggest that some loci may influence the clinical outcome of malaria.
Signal transducer and activator of transcription 3 activation is associated with bladder cancer cell growth and survival
Authors: Chen Chun-Liang , Cen Ling , Kohout Jennifer , Hutzen Brian , Chan Christina , Hsieh Fu-Chuan , Loy Abbey , Huang Victor , Cheng Gong , Lin Jiayuh
Published: October 2008

Background

Constitutive activation of signal transducer and activator of transcription 3 (Stat3) signaling pathway plays an important role in several human cancers. Activation of Stat3 is dependent on the phosphorylation at the tyrosine residue 705 by upstream kinases and subsequent nuclear translocation after dimerization. It remains unclear whether oncogenic Stat3 signaling pathway is involved in the oncogenesis of bladder cancer.

Results

We found that elevated Stat3 phosphorylation in 19 of 100 (19%) bladder cancer tissues as well as bladder cancer cell lines, WH, UMUC-3 and 253J. To explore whether Stat3 activation is associated with cell growth and survival of bladder cancer, we targeted the Stat3 signaling pathway in bladder cancer cells using an adenovirus-mediated dominant-negative Stat3 (Y705F) and a small molecule compound, STA-21. Both prohibited cell growth and induction of apoptosis in these bladder cancer cell lines but not in normal bladder smooth muscle cell (BdSMC). The survival inhibition might be mediated through apoptotic caspase 3, 8 and 9 pathways. Moreover, down-regulation of anti-apoptotic genes (Bcl-2, Bcl-xL and survivin) and a cell cycle regulating gene (cyclin D1) was associated with the cell growth inhibition and apoptosis.

Conclusion

These results indicated that activation of Stat3 is crucial for bladder cancer cell growth and survival. Therefore, interference of Stat3 signaling pathway emerges as a potential therapeutic approach for bladder cancer.
Rhabdomyosarcoma cells show an energy producing anabolic metabolic phenotype compared with primary myocytes
Authors: Fan Teresa WM , Kucia Magda , Jankowski Kacper , Higashi Richard M , Ratajczak Janina , Ratajczak Marius Z , Lane Andrew N
Published: October 2008

Background

The functional status of a cell is expressed in its metabolic activity. We have applied stable isotope tracing methods to determine the differences in metabolic pathways in proliferating Rhabdomysarcoma cells (Rh30) and human primary myocytes in culture. Uniformly 13C-labeled glucose was used as a source molecule to follow the incorporation of 13C into more than 40 marker metabolites using NMR and GC-MS. These include metabolites that report on the activity of glycolysis, Krebs' cycle, pentose phosphate pathway and pyrimidine biosynthesis.

Results

The Rh30 cells proliferated faster than the myocytes. Major differences in flux through glycolysis were evident from incorporation of label into secreted lactate, which accounts for a substantial fraction of the glucose carbon utilized by the cells. Krebs' cycle activity as determined by 13C isotopomer distributions in glutamate, aspartate, malate and pyrimidine rings was considerably higher in the cancer cells than in the primary myocytes. Large differences were also evident in de novo biosynthesis of riboses in the free nucleotide pools, as well as entry of glucose carbon into the pyrimidine rings in the free nucleotide pool. Specific labeling patterns in these metabolites show the increased importance of anaplerotic reactions in the cancer cells to maintain the high demand for anabolic and energy metabolism compared with the slower growing primary myocytes. Serum-stimulated Rh30 cells showed higher degrees of labeling than serum starved cells, but they retained their characteristic anabolic metabolism profile. The myocytes showed evidence of de novo synthesis of glycogen, which was absent in the Rh30 cells.

Conclusion

The specific 13C isotopomer patterns showed that the major difference between the transformed and the primary cells is the shift from energy and maintenance metabolism in the myocytes toward increased energy and anabolic metabolism for proliferation in the Rh30 cells. The data further show that the mitochondria remain functional in Krebs' cycle activity and respiratory electron transfer that enables continued accelerated glycolysis. This may be a common adaptive strategy in cancer cells.
Size dependent heat generation of magnetite nanoparticles under AC magnetic field for cancer therapy
Authors: Motoyama Jun , Hakata Toshiyuki , Kato Ryuji , Yamashita Noriyuki , Morino Tomio , Kobayashi Takeshi , Honda Hiroyuki
Published: October 2008

Background

We have developed magnetic cationic liposomes (MCLs) that contained magnetic nanoparticles as heating mediator for applying them to local hyperthermia. The heating performance of the MCLs is significantly affected by the property of the incorporated magnetite nanoparticles. We estimated heating capacity of magnetite nanoparticles by measuring its specific absorption rate (SAR) against irradiation of the alternating magnetic field (AMF).

Method

Magnetite nanoparticles which have various specific-surface-area (SSA) are dispersed in the sample tubes, subjected to various AMF and studied SAR.

Result

Heat generation of magnetite particles under variable AMF conditions was summarized by the SSA. There were two maximum SAR values locally between 12 m2/g to 190 m2/g of the SSA in all ranges of applied AMF frequency and those values increased followed by the intensity of AMF power. One of the maximum values was observed at approximately 90 m2/g of the SSA particles and the other was observed at approximately 120 m2/g of the SSA particles. A boundary value of the SAR for heat generation was observed around 110 m2/g of SSA particles and the effects of the AMF power were different on both hand. Smaller SSA particles showed strong correlation of the SAR value to the intensity of the AMF power though larger SSA particles showed weaker correlation.

Conclusion

Those results suggest that two maximum SAR value stand for the heating mechanism of magnetite nanoparticles represented by hysteresis loss and relaxation loss.
Protective CD8+ T-cell responses to cytomegalovirus driven by rAAV/GFP/IE1 loading of dendritic cells
Authors: Yu Yuefei , Pilgrim Petra , Yan Juqiang , Zhou Wei , Jenkins Marjorie , Gagliano Nicoletta , Bumm Klaus , Cannon Martin , Milzani Aldo , Dalle-Donne Isabella , Kast W Martin , Cobos Everardo , Chiriva-Internati Maurizio
Published: October 2008

Background

Recent studies demonstrate that recombinant adeno-associated virus (rAAV)-based antigen loading of dendritic cells (DCs) generatesin vitro, significant and rapid cytotoxic T-lymphocyte (CTL) responses against viral antigens.

Methods

We used the rAAV system to induce specific CTLs against CVM antigens for the development of cytomegalovirus HCMV) gene therapy. As an extension of the versatility of the rAAV system, we incorporated immediate-early 1 (IE1), expressed in HCMV. Our rAAV vector induced a strong stimulation of CTLs directed against the HCMV antigen IE1. We then investigated the efficiency of the CTLs in killing IE1 targeted cells.

Results

A significant MHC Class I-restricted, anti-IE1-specific CTL killing was demonstrated against IE1 positive peripheral blood mononuclear cells (PBMC) after one,in vitro, stimulation.

Conclusion

In summary, single PBMC stimulation with rAAV/IE1 pulsed DCs induces strong antigen specific-CTL generation. CTLs were capable to lyse low doses of peptides pulsed into target cells. These data suggest that AAV-based antigen loading of DCs is highly effective for generating human CTL responses against HCMV antigens.