bluuebunny/crossref_metadata_2025 huggingface dataset:
High Loosening Rate of the Moje Acamo Prosthesis for Treating Osteoarthritis of the Trapeziometacarpal Joint
Authors: HANSEN T. B. , VAINORIUS D.
Published: August 2008

The Moje Acamo carpometacarpal (CMC) implant is an uncemented large ball-and-socket joint made of a ceramic material coated with a bioactive substance (Bioverit) for osseous fixation. Nine Moje Acamo CMC prostheses were implanted into nine patients with primary osteoarthritis of the thumb CMC joint. At 12 months, three implants had been revised because of progressing pain and osteolysis. In the remaining six patients, radiographs have shown progressive osteolysis around both implants in five patients.

These poor results mean that we no longer perform this operation and we recommend close follow-up of all cases that have been performed.
Transverse Loaded Pronosupination Test
Authors: GARCIA-ELIAS M. , LLUCH A. L. , FERRERES A. , LLUCH A. , LHAMBY F.
Published: August 2008

A new test to evaluate the ability of the distal radioulnar joint to sustain transverse loads while the forearm rotates from pronation to supination is described. Both arms were tested in 100 normal volunteers. The average weight-bearing capability of the normal unsupported forearm was 5.07 kg, equating to a force of 49.8 N. The test may be useful in the assessment of pathological conditions involving weakness of the forearm rotator muscles, with or without joint incongruity, as well as being an indirect way to assess the load-bearing capacity of radioulnar implants.
Complex Extensor Tendon Injuries: Early Active Motion Following Single-Stage Reconstruction
Authors: KOUL A. R. , PATIL R. K. , PHILIP V.
Published: August 2008

This study presents a retrospective evaluation of patients managed with single-stage repair following complex extensor tendon injuries. Over a 2-year period, 21 extensor tendons were reconstructed in 18 patients with complex hand injuries in zones V–VII. All eight patients needed soft tissue cover. Active mobilisation was started in the first week.

Total active motion (TAM) at 4 weeks was a mean of 159° (SD 21.57) and at 6 weeks it was 202.6° (SD 13.26). Average TAM at 8 weeks was 223.8° (SD 16.46) and 249.5° (SD 14.38) at 12 weeks. Grip strength at 12 weeks and 6 months was around 75% and 90% of the contralateral normal hand in most of the patients.

Single-stage reconstruction of complex extensor tendon injuries seems to reduce morbidity in terms of hospitalisation, and reduced cost of treatment. It also helps to achieve better functional outcome in the early postoperative period.
Correction of Swan Neck Deformity in Rheumatoid Arthritis Using a New Lateral Extensor Band Technique
Authors: SIROTAKOVA M. , FIGUS A. , JARRETT P. , MISHRA A. , ELLIOT D.
Published: August 2008

Swan neck deformity is a progressive and disabling condition that commonly affects rheumatoid arthritic hands. During a 4-year period, 101 fingers in 43 patients had this deformity corrected using a new procedure combining the distally based extensor lateral band technique described by Littler and the flexor digitorum superficialis (FDS)-palmar plate pulley introduced by Zancolli. The ranges of motion of the metacarpophalangeal, proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints were assessed pre-operatively and 12 months after surgery. An average PIP joint hyperextension of −13.3° was converted to +13.4°. The ranges of motion of the proximal and DIP joints were significantly different (Student’s t-test). No patient suffered recurrence of the deformity during an average follow-up of 20 months. This new technique improves some unappealing aspects of previous techniques and provides a stable and reliable correction of swan neck deformity.
Influence of ZnO homobuffer layer on n-ZnO/p-Si photodiode
Authors: Qi H. X. , Li Q. S. , Zhao B. , Zheng M. M. , Li X. S. , Zhang N.
Published: August 2008

We investigate the n-ZnO/p-Si heterojunction photodiodes which were fabricated by pulsed laser deposition of ZnO films on p-Si substrate. A ZnO thin layer deposited at 200°C in oxygen free ambient was used as a buffer layer for the subsequent ZnO growth. The influence of ZnO homobuffer layer on n-ZnO/p-Si photodiode was studied. The results obtained by X-ray diffraction and atomic force microscopy showed that ZnO film with a homobuffer layer had better crystallinity and a smoother surface than the film without the buffer layer. As characterised by current–voltage (I–V) measurements, the dark leakage current of the buffered sample decreased significantly. Under Xe arc lamp illumination of 670 nm, photoresponsivity of 0˙28 A W–1 and quantum efficiency of 48% at 5 V reverse bias were obtained from the photodiode with ZnO homobuffer layer.
PEBP2-β/CBF-β–dependent phosphorylation of RUNX1 and p300 by HIPK2: implications for leukemogenesis
Authors: Wee Hee-Jun , Voon Dominic Chih-Cheng , Bae Suk-Chul , Ito Yoshiaki
Published: August 2008

The heterodimeric transcription factor RUNX1/PEBP2-β (also known as AML1/CBF-β) is essential for definitive hematopoiesis. Here, we show that interaction with PEBP2-β leads to the phosphorylation of RUNX1, which in turn induces p300 phosphorylation. This is mediated by homeodomain interacting kinase 2 (HIPK2), targeting Ser249, Ser273, and Thr276 in RUNX1, in a manner that is also dependent on the RUNX1 PY motif. Importantly, we observed the in vitro disruption of this phosphorylation cascade by multiple leukemogenic genetic defects targeting RUNX1/CBFB. In particular, the oncogenic protein PEBP2-β-SMMHC prevents RUNX1/p300 phosphorylation by sequestering HIPK2 to mislocalized RUNX1/β-SMMHC complexes. Therefore, phosphorylation of RUNX1 appears a critical step in its association with and phosphorylation of p300, and its disruption may be a common theme in RUNX1-associated leukemogenesis.
Stat5 regulates cellular iron uptake of erythroid cells via IRP-2 and TfR-1
Authors: Kerenyi Marc A. , Grebien Florian , Gehart Helmuth , Schifrer Manfred , Artaker Matthias , Kovacic Boris , Beug Hartmut , Moriggl Richard , Müllner Ernst W.
Published: August 2008

Erythropoiesis strictly depends on signal transduction through the erythropoietin receptor (EpoR)–Janus kinase 2 (Jak2)–signal transducer and activator of transcription 5 (Stat5) axis, regulating proliferation, differentiation, and survival. The exact role of the transcription factor Stat5 in erythropoiesis remained puzzling, however, since the first Stat5-deficient mice carried a hypomorphic Stat5 allele, impeding full phenotypical analysis. Using mice completely lacking Stat5—displaying early lethality—we demonstrate that these animals suffer from microcytic anemia due to reduced expression of the antiapoptotic proteins Bcl-xL and Mcl-1 followed by enhanced apoptosis. Moreover, transferrin receptor-1 (TfR-1) cell surface levels on erythroid cells were decreased more than 2-fold on erythroid cells of Stat5−/− animals. This reduction could be attributed to reduced transcription of TfR-1 mRNA and iron regulatory protein 2 (IRP-2), the major translational regulator of TfR-1 mRNA stability in erythroid cells. Both genes were demonstrated to be direct transcriptional targets of Stat5. This establishes an unexpected mechanistic link between EpoR/Jak/Stat signaling and iron metabolism, processes absolutely essential for erythropoiesis and life.
Exhaustive prediction of disease susceptibility to coding base changes in the human genome
Authors: Kulkarni Vinayak , Errami Mounir , Barber Robert , Garner Harold R
Published: August 2008

Background

Single Nucleotide Polymorphisms (SNPs) are the most abundant form of genomic variation and can cause phenotypic differences between individuals, including diseases. Bases are subject to various levels of selection pressure, reflected in their inter-species conservation.

Results

We propose a method that is not dependant on transcription information to score each coding base in the human genome reflecting the disease probability associated with its mutation. Twelve factors likely to be associated with disease alleles were chosen as the input for a support vector machine prediction algorithm. The analysis yielded 83% sensitivity and 84% specificity in segregating disease like alleles as found in the Human Gene Mutation Database from non-disease like alleles as found in the Database of Single Nucleotide Polymorphisms. This algorithm was subsequently applied to each base within all known human genes, exhaustively confirming that interspecies conservation is the strongest factor for disease association. For each gene, the length normalized average disease potential score was calculated. Out of the 30 genes with the highest scores, 21 are directly associated with a disease. In contrast, out of the 30 genes with the lowest scores, only one is associated with a disease as found in published literature. The results strongly suggest that the highest scoring genes are enriched for those that might contribute to disease, if mutated.

Conclusion

This method provides valuable information to researchers to identify sensitive positions in genes that have a high disease probability, enabling them to optimize experimental designs and interpret data emerging from genetic and epidemiological studies.
ProteoLens: a visual analytic tool for multi-scale database-driven biological network data mining
Authors: Huan Tianxiao , Sivachenko Andrey Y , Harrison Scott H , Chen Jake Y
Published: August 2008

Background

New systems biology studies require researchers to understand how interplay among myriads of biomolecular entities is orchestrated in order to achieve high-level cellular and physiological functions. Many software tools have been developed in the past decade to help researchers visually navigate large networks of biomolecular interactions with built-in template-based query capabilities. To further advance researchers' ability to interrogate global physiological states of cells through multi-scale visual network explorations, new visualization software tools still need to be developed to empower the analysis. A robust visual data analysis platform driven by database management systems to perform bi-directional data processing-to-visualizations with declarative querying capabilities is needed.

Results

We developed ProteoLens as a JAVA-based visual analytic software tool for creating, annotating and exploring multi-scale biological networks. It supports direct database connectivity to either Oracle or PostgreSQL database tables/views, on which SQL statements using both Data Definition Languages (DDL) and Data Manipulation languages (DML) may be specified. The robust query languages embedded directly within the visualization software help users to bring their network data into a visualization context for annotation and exploration. ProteoLens supports graph/network represented data in standard Graph Modeling Language (GML) formats, and this enables interoperation with a wide range of other visual layout tools. The architectural design of ProteoLens enables the de-coupling of complex network data visualization tasks into two distinct phases: 1) creating network data association rules, which are mapping rules between network node IDs or edge IDs and data attributes such as functional annotations, expression levels, scores, synonyms, descriptions etc; 2) applying network data association rules to build the network and perform the visual annotation of graph nodes and edges according to associated data values. We demonstrated the advantages of these new capabilities through three biological network visualization case studies: human disease association network, drug-target interaction network and protein-peptide mapping network.

Conclusion

The architectural design of ProteoLens makes it suitable for bioinformatics expert data analysts who are experienced with relational database management to perform large-scale integrated network visual explorations. ProteoLens is a promising visual analytic platform that will facilitate knowledge discoveries in future network and systems biology studies.
Very Important Pool (VIP) genes – an application for microarray-based molecular signatures
Authors: Su Zhenqiang , Hong Huixiao , Fang Hong , Shi Leming , Perkins Roger , Tong Weida
Published: August 2008

Background

Advances in DNA microarray technology portend that molecular signatures from which microarray will eventually be used in clinical environments and personalized medicine. Derivation of biomarkers is a large step beyond hypothesis generation and imposes considerably more stringency for accuracy in identifying informative gene subsets to differentiate phenotypes. The inherent nature of microarray data, with fewer samples and replicates compared to the large number of genes, requires identifying informative genes prior to classifier construction. However, improving the ability to identify differentiating genes remains a challenge in bioinformatics.

Results

A new hybrid gene selection approach was investigated and tested with nine publicly available microarray datasets. The new method identifies a Very Important Pool (VIP) of genes from the broad patterns of gene expression data. The method uses a bagging sampling principle, where the re-sampled arrays are used to identify the most informative genes. Frequency of selection is used in a repetitive process to identify the VIP genes. The putative informative genes are selected using two methods, t-statistic and discriminatory analysis. In the t-statistic, the informative genes are identified based on p-values. In the discriminatory analysis, disjoint Principal Component Analyses (PCAs) are conducted for each class of samples, and genes with high discrimination power (DP) are identified. The VIP gene selection approach was compared with the p-value ranking approach. The genes identified by the VIP method but not by the p-value ranking approach are also related to the disease investigated. More importantly, these genes are part of the pathways derived from the common genes shared by both the VIP and p-ranking methods. Moreover, the binary classifiers built from these genes are statistically equivalent to those built from the top 50 p-value ranked genes in distinguishing different types of samples.

Conclusion

The VIP gene selection approach could identify additional subsets of informative genes that would not always be selected by the p-value ranking method. These genes are likely to be additional true positives since they are a part of pathways identified by the p-value ranking method and expected to be related to the relevant biology. Therefore, these additional genes derived from the VIP method potentially provide valuable biological insights.
Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer
Authors: FitzGerald Liesel M , Agalliu Ilir , Johnson Karynn , Miller Melinda A , Kwon Erika M , Hurtado-Coll Antonio , Fazli Ladan , Rajput Ashish B , Gleave Martin E , Cox Michael E , Ostrander Elaine A , Stanford Janet L , Huntsman David G
Published: August 2008

Background

The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer.

Methods

In this study, fluorescentin situhybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of fourERGand oneTMPRSS2SNPs using germline DNA was also performed in a sample of the cases (n = 127).

Results

Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22–3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23–3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45–3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of theTMPRSS2SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03).

Conclusion

If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.
EGFR and HER2 expression in primary cervical cancers and corresponding lymph node metastases: Implications for targeted radiotherapy
Authors: Shen Li , Shui Yongjie , Wang Xiaojia , Sheng Liming , Yang Zhengyan , Xue Danfeng , Wei Qichun
Published: August 2008

Background

Proteins overexpressed on the surface of tumor cells can be selectively targeted. Epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) are among the most often targeted proteins. The level and stability of expression in both primary tumors and corresponding metastases is crucial in the assessment of a receptor as target for imaging in nuclear medicine and for various forms of therapy. So far, the expression of EGFR and HER2 has only been determined in primary cervical cancers, and we have not found published data regarding the receptor status in corresponding metastatic lesions. The goal of this study was to evaluate whether any of these receptors are suitable as target for clinical diagnosis and therapy.

Methods

Expression of EGFR and HER2 was investigated immunohistochemically in both lymph node metastases and corresponding primary cervical cancers (n = 53). HER2 and EGFR expression was scored using HercepTest criteria (0, 1+, 2+ or 3+).

Results

EGFR overexpression (2+ or 3+) was found in 64% (35/53) of the primary cervical tumors and 60% (32/53) of the corresponding lymph node metastases. There was a good concordance between the primary tumors and the paired metastases regarding EGFR expression. Only four patients who had 2+ or 3+ in the primary tumors changed to 0 or 1+ in lymph node metastases, and another two cases changed the other way around. None of the primary tumors or the lymph node metastases expressed HER2 protein.

Conclusion

The EGFR expression seems to be common and stable during cervical cancer metastasis, which is encouraging for testing of EGFR targeted radiotherapy. HER2 appears to be of poor interest as a potential target in the treatment of cervical cancer.
Human eosinophil adhesion and degranulation stimulated with eotaxin and RANTES in vitro: Lack of interaction with nitric oxide
Authors: Lintomen Letícia , Franchi Gilberto , Nowill Alexandre , Condino-Neto Antonio , de Nucci Gilberto , Zanesco Angelina , Antunes Edson
Published: August 2008

Background

Airway eosinophilia is considered a central event in the pathogenesis of asthma. The toxic components of eosinophils are thought to be important in inducing bronchial mucosal injury and dysfunction. Previous studies have suggested an interaction between nitric oxide (NO) and chemokines in modulating eosinophil functions, but this is still conflicting. In the present study, we have carried out functional assays (adhesion and degranulation) and flow cytometry analysis of adhesion molecules (VLA-4 and Mac-1 expression) to evaluate the interactions between NO and CC-chemokines (eotaxin and RANTES) in human eosinophils.

Methods

Eosinophils were purified using a percoll gradient followed by immunomagnetic cell separator. Cell adhesion and degranulation were evaluated by measuring eosinophil peroxidase (EPO) activity, whereas expression of Mac-1 and VLA-4 was detected using flow cytometry.

Results

At 4 h incubation, both eotaxin (100 ng/ml) and RANTES (1000 ng/ml) increased by 133% and 131% eosinophil adhesion, respectively. L-NAME alone (but not D-NAME) also increased the eosinophil adhesion, but the co-incubation of L-NAME with eotaxin or RANTES did not further affect the increased adhesion seen with chemokines alone. In addition, L-NAME alone (but not D-NAME) caused a significant cell degranulation, but it did not affect the CC-chemokine-induced cell degranulation. Incubation of eosinophils with eotaxin or RANTES, in absence or presence of L-NAME, did not affect the expression of VLA-4 and Mac-1 on eosinophil surface. Eotaxin and RANTES (100 ng/ml each) also failed to elevate the cyclic GMP levels above baseline in human eosinophils.

Conclusion

Eotaxin and RANTES increase the eosinophil adhesion to fibronectin-coated plates and promote cell degranulation by NO-independent mechanisms. The failure of CC-chemokines to affect VLA-4 and Mac-1 expression suggests that changes in integrin function (avidity or affinity) are rather involved in the enhanced adhesion.
Dissatisfaction with the laboratory services in conducting HIV related testing among public and private medical personnel in Tanzania
Authors: Mfinanga SG , Kahwa A , Kimaro G , Kilale A , Kivuyo S , Senkoro M , Ngowi B , Mtandu R , Mutayoba B , Ngadaya E , Mashoto K
Published: August 2008

Background

A comprehensive care and treatment program requires a well functioning laboratory services. We assessed satisfaction of medical personnel to the laboratory services to guide process of quality improvement of the services.

Methodology

A cross-sectional survey in 24 randomly selected health facilities in Mainland Tanzania was conducted to assess the satisfaction of the medical personnel with the laboratory services.

Results

Of 235 medical personnel interviewed, 196 were valid for analysis and about one quarter were dissatisfied with the laboratory services. Personnel dissatisfied with the services were 38.3% in timely test result, 24.5% in correct and accurate results and 22.4% in clear complete results. The personnel in public laboratories were more dissatisfied with timely test results (OR = 3.6, 95% CI 1.8, 7.3), correct results (OR = 4.1, 95% CI 1.6, 10.8) and clear complete results (OR = 5.0 95% CI 1.6, 15.2). Personnel dissatisfied with the services in 15 laboratories sending specimens to referral laboratories, varied from 13% in availability of equipment to 57% in timely results feedback from the referral laboratories. Personnel dissatisfied with the services in 14 referral laboratories, varied from 28.6% in properly identified specimen to 42.9% in clear, accurate test request and communication.

Conclusion

About one quarter of medical personnel in sending or receiving laboratories were dissatisfied with the services. Comparing the personnel in public and private, the personnel in public laboratories were 4 times more dissatisfied with the timely test and correct results; and 5 times more dissatisfied with clear and complete test results.
In vivo quantification of embryonic and placental growth during gestation in mice using micro-ultrasound
Authors: Mu Junwu , Slevin John C , Qu Dawei , McCormick Sarah , Adamson S Lee
Published: August 2008

Background

Non-invasive micro-ultrasound was evaluated as a method to quantify intrauterine growth phenotypes in mice. Improved methods are required to accelerate research using genetically-altered mice to investigate the interactive roles of genes and environments on embryonic and placental growth. We determined (1) feasible age ranges for measuring specific variables, (2) normative growth curves, (3) accuracy of ultrasound measurements in comparison with light microscopy, and (4) weight prediction equations using regression analysis for CD-1 mice and evaluated their accuracy when applied to other mouse strains.

Methods

We used 30–40 MHz ultrasound to quantify embryonic and placental morphometry in isoflurane-anesthetized pregnant CD-1 mice from embryonic day 7.5 (E7.5) to E18.5 (full-term), and for C57Bl/6J, B6CBAF1, and hIGFBP1 pregnant transgenic mice at E17.5.

Results

Gestational sac dimension provided the earliest measure of conceptus size. Sac dimension derived using regression analysis increased from 0.84 mm at E7.5 to 6.44 mm at E11.5 when it was discontinued. The earliest measurement of embryo size was crown-rump length (CRL) which increased from 1.88 mm at E8.5 to 16.22 mm at E16.5 after which it exceeded the field of view. From E10.5 to E18.5 (full term), progressive increases were observed in embryonic biparietal diameter (BPD) (0.79 mm to 7.55 mm at E18.5), abdominal circumference (AC) (4.91 mm to 26.56 mm), and eye lens diameter (0.20 mm to 0.93 mm). Ossified femur length was measureable from E15.5 (1.06 mm) and increased linearly to 2.23 mm at E18.5. In contrast, placental diameter (PD) and placental thickness (PT) increased from E10.5 to E14.5 then remained constant to term in accord with placental weight. Ultrasound and light microscopy measurements agreed with no significant bias and a discrepancy of less than 25%. Regression equations predicting gestational age from individual variables, and embryonic weight (BW) from CRL, BPD, and AC were obtained. The prediction equation BW = -0.757 + 0.0453 (CRL) + 0.0334 (AC) derived from CD-1 data predicted embryonic weights at E17.5 in three other strains of mice with a mean discrepancy of less than 16%.

Conclusion

Micro-ultrasound provides a feasible tool for in vivo morphometric quantification of embryonic and placental growth parameters in mice and for estimation of embryonic gestational age and/or body weight in utero.
Why did soft drink consumption decrease but screen time not? Mediating mechanisms in a school-based obesity prevention program
Authors: Chin A Paw Marijke JM , Singh Amika S , Brug Johannes , van Mechelen Willem
Published: August 2008

Objectives

This paper aims to identify the mediating mechanisms of a school-based obesity prevention program (DOiT).

Methods

The DOiT-program was implemented in Dutch prevocational secondary schools and evaluated using a controlled, cluster-randomised trial (September 2003 to May 2004). We examined mediators of effects regarding (1) consumption of sugar containing beverages (SCB); (2) consumption of high caloric snacks; (3) screen-viewing behaviour; and (4) active commuting to school. To improve these behaviours the DOiT-program tried to influence the following potentially mediating variables: attitude, subjective norm, perceived behavioural control, and habit-strength.

Results

Both in boys (n = 418) and girls (n = 436) the DOiT-intervention reduced SCB consumption (between group difference in boys = -303.5 ml/day, 95% CI: -502.4;-104.5, between group difference in girls = -222.3 ml/day, 95% CI: -371.3;-73.2). The intervention did not affect the other examined behaviours. In girls, no intervention effect on hypothetical mediators was found nor evidence of any mediating mechanisms. Boys in intervention schools improved their attitude towards decreasing SCB consumption, while this behaviour became less of a habit. Indeed, attitude and habit strength were significant mediators of the DOiT-intervention's effect (4.5 and 3.8%, respectively) on SCB consumption among boys.

Conclusion

Our findings imply that interventions aimed at EBRB-change should be gender-specific. Future studies aimed at reducing SCB consumption among boys should target attitude and habit strength as mediating mechanisms. Our study did not resolve the mediating mechanisms in girls.

Trial registration

International Standard Randomised Controlled Trial Number Register ISRCTN87127361
Modulation of Chloride Homeostasis by Inflammatory Mediators in Dorsal Root Ganglion Neurons
Authors: Funk Katharina , Woitecki Anne , Franjic-Würtz Christina , Gensch Thomas , Möhrlen Frank , Frings Stephan
Published: August 2008

Background:

Chloride currents in peripheral nociceptive neurons have been implicated in the generation of afferent nociceptive signals, as Cl− accumulation in sensory endings establishes the driving force for depolarizing, and even excitatory, Cl− currents. The intracellular Cl− concentration can, however, vary considerably between individual DRG neurons. This raises the question, whether the contribution of Cl− currents to signal generation differs between individual afferent neurons, and whether the specific Cl− levels in these neurons are subject to modulation. Based on the hypothesis that modulation of the peripheral Cl− homeostasis is involved in the generation of inflammatory hyperalgesia, we examined the effects of inflammatory mediators on intracellular Cl− concentrations and on the expression levels of Cl− transporters in rat DRG neurons.

Results:

We developed an in vitro assay for testing how inflammatory mediators influence Cl− concentration and the expression of Cl− transporters. Intact DRGs were treated with 100 ng/ml NGF, 1.8 μM ATP, 0.9 μM bradykinin, and 1.4 μM PGE2 for 1–3 hours. Two-photon fluorescence lifetime imaging with the Cl−-sensitive dye MQAE revealed an increase of the intracellular Cl− concentration within 2 hours of treatment. This effect coincided with enhanced phosphorylation of the Na+-K+−2Cl− cotransporter NKCC1, suggesting that an increased activity of that transporter caused the early rise of intracellular Cl− levels. Immunohistochemistry of NKCC1 and KCC2, the main neuronal Cl− importer and exporter, respectively, exposed an inverse regulation by the inflammatory mediators. While the NKCC1 immunosignal increased, that of KCC2 declined after 3 hours of treatment. In contrast, the mRNA levels of the two transporters did not change markedly during this time. These data demonstrate a fundamental transition in Cl− homeostasis toward a state of augmented Cl− accumulation, which is induced by a 1–3 hour treatment with inflammatory mediators.

Conclusion:

Our findings indicate that inflammatory mediators impact on Cl− homeostasis in DRG neurons. Inflammatory mediators raise intracellular Cl− levels and, hence, the driving force for depolarizing Cl− efflux. These findings corroborate current concepts for the role of Cl− regulation in the generation of inflammatory hyperalgesia and allodynia. As the intracellular Cl− concentration rises in DRG neurons, afferent signals can be boosted by excitatory Cl− currents in the presynaptic terminals. Moreover, excitatory Cl− currents in peripheral sensory endings may also contribute to the generation or modulation of afferent signals, especially in inflamed tissue.
Infraorbital cutaneous angiosarcoma: a diagnostic and therapeutic dilemma
Authors: Ettl Tobias , Kleinheinz Johannes , Mehrotra Ravi , Schwarz Stephan , Reichert Torsten E , Driemel Oliver
Published: August 2008

Background

A cutaneous angiosarcoma is a rare malignant tumour of vascular endothelial cells with aggressive clinical behaviour and poor prognosis. Diagnosis is often delayed due to its variable and often benign clinical appearance.

Case presentation

This case presents a 64-year-old man with a six-month-history of a recurrent diffuse and erythematous painless swelling below the left eye. Several resections with intraoperatively negative resection margins followed, but positive margins were repeatedly detected later on permanent sections. Histopathologic examination of the specimen diagnosed a cutaneous angiosarcoma. Neither, finally achieved negative margins on permanent sections, nor a following chemotherapy could prevent the recurrence of the disease after five months and the patient's dead 21 months after the first diagnosis.

Conclusion

The case elucidates the current diagnostic and therapeutic dilemma of this entity, which shows an unfavourable clinical course in spite of multimodal therapy.
Role of Caveolin 1, E-Cadherin, Enolase 2 and PKCalpha on resistance to methotrexate in human HT29 colon cancer cells
Authors: Selga Elisabet , Morales Cristina , Noé Véronique , Peinado Miguel A , Ciudad Carlos J
Published: August 2008

Background

Methotrexate is one of the earliest cytotoxic drugs used in cancer therapy, and despite the isolation of multiple other folate antagonists, methotrexate maintains its significant role as a treatment for different types of cancer and other disorders. The usefulness of treatment with methotrexate is limited by the development of drug resistance, which may be acquired through different ways. To get insights into the mechanisms associated with drug resistance and sensitization we performed a functional analysis of genes deregulated in methotrexate resistant cells, either due to its co-amplification with thedhfrgene or as a result of a transcriptome screening using microarrays.

Methods

Gene expression levels were compared between triplicate samples from either HT29 sensitive cells and resistant to 10-5M MTX by hybridization to the GeneChip®HG U133 PLUS 2.0 from Affymetrix. After normalization, a list of 3-fold differentially expressed genes with a p-value < 0.05 including multiple testing correction (Benjamini and Hochberg false discovery rate) was generated. RT-Real-time PCR was used to validate the expression levels of selected genes and copy-number was determined by qPCR. Functional validations were performed either by siRNAs or by transfection of an expression plasmid.

Results

Genes adjacent to thedhfr locusand included in the 5q14 amplicon were overexpressed in HT29 MTX-resistant cells. Treatment with siRNAs against those genes caused a slight reduction in cell viability in both HT29 sensitive and resistant cells. On the other hand, microarray analysis of HT29 and HT29 MTX resistant cells unveiled overexpression of caveolin 1, enolase 2 and PKCα genes in resistant cells without concomitant copy number gain. siRNAs against these three genes effectively reduced cell viability and caused a decreased MTX resistance capacity. Moreover, overexpression of E-cadherin, which was found underexpressed in MTX-resistant cells, also sensitized the cells toward the chemotherapeutic agent. Combined treatments targeting siRNA inhibition of caveolin 1 and overexpression of E-cadherin markedly reduced cell viability in both sensitive and MTX-resistant HT29 cells.

Conclusion

We provide functional evidences indicating that caveolin 1 and E-cadherin, deregulated in MTX resistant cells, may play a critical role in cell survival and may constitute potential targets for coadjuvant therapy.
Growing pains: contemporary knowledge and recommended practice
Authors: Evans Angela M
Published: August 2008

Background

Leg pain in children, described as growing pains, is a frequent clinical presentation seen by an array of health care professionals. Described since 1823, growing pains continues to puzzle practitioners, yet diagnostic criteria and evidence based treatment is available.

Methods

The medical literature has been searched exhaustively to access all articles (English language) pertaining to leg pains in children which are ascribed to being ‘growing pains’.

Results

The literature, whilst plentiful in quantity and spanning two centuries, is generally replete with reiterated opinion and anecdote and lacking in scientific rigour. The author searched 45 articles for relevance, determined according to title, abstract and full text, resulting in a yield of 22 original studies and 23 review articles. From the original studies, one small (non‐blinded) randomised controlled trial that focused on GP treatment with leg muscle stretching was found. Nine prevalence studies were found revealing disparate estimates. Ten cohort (some case‐controlled) studies, which investigated pain attribute differences in affected versus unaffected groups, were found. One series of single case experiment designs and one animal model study were found.

Conclusion

Growing pains is prevalent in young children, presents frequently in the health care setting where it is poorly managed and is continuing to be researched. A common childhood complaint, growing pains needs to be acknowledged and better managed in the contemporary medical setting.
Limb body wall complex in a still born fetus: a case report
Authors: Plakkal Nishad , John Joseph , Jacob Sajini Elizabeth , Chithira J , Sampath Sowmya
Published: August 2008

We report the case of a male, low birth weight, stillborn fetus of 36 weeks gestation with limb body wall complex. An interesting and rare feature noted in the propositus was the absence of the left subclavian artery and complete absence of the left upper limb. These findings seem to favor the vascular theory in the pathogenesis of this condition.
Genomic analysis of the relationship between gene expression variation and DNA polymorphism in Drosophila simulans
Authors: Lawniczak Mara KN , Holloway Alisha K , Begun David J , Jones Corbin D
Published: August 2008

Background

Understanding how DNA sequence polymorphism relates to variation in gene expression is essential to connecting genotypic differences with phenotypic differences among individuals. Addressing this question requires linking population genomic data with gene expression variation.

Results

Using whole genome expression data and recent light shotgun genome sequencing of six Drosophila simulans genotypes, we assessed the relationship between expression variation in males and females and nucleotide polymorphism across thousands of loci. By examining sequence polymorphism in gene features, such as untranslated regions and introns, we find that genes showing greater variation in gene expression between genotypes also have higher levels of sequence polymorphism in many gene features. Accordingly, X-linked genes, which have lower sequence polymorphism levels than autosomal genes, also show less expression variation than autosomal genes. We also find that sex-specifically expressed genes show higher local levels of polymorphism and divergence than both sex-biased and unbiased genes, and that they appear to have simpler regulatory regions.

Conclusion

The gene-feature-based analyses and the X-to-autosome comparisons suggest that sequence polymorphism in cis-acting elements is an important determinant of expression variation. However, this relationship varies among the different categories of sex-biased expression, and trans factors might contribute more to male-specific gene expression than cis effects. Our analysis of sex-specific gene expression also shows that female-specific genes have been overlooked in analyses that only point to male-biased genes as having unusual patterns of evolution and that studies of sexually dimorphic traits need to recognize that the relationship between genetic and expression variation at these traits is different from the genome as a whole.
Motherhood and Childlessness in Monozygous Twins
Authors: Malmquist A. , Kaij L.
Published: August 2008

The first part of this study of female monozygous twins discordant for childbirth covered intrapair differences before pregnancy (Kaij and Malmquist, 1970). This part is focused on the influence of motherhood on health, presented as intrapair differences in gynaecological, other somatic, and psychiatric morbidity after pregnancy.
Psychoses in the Offspring of Schizophrenic Monozygotic Twins and their Normal Co-Twins
Authors: Fischer Margit
Published: August 2008

The difficulty of examining separately the genetic and environmental factors responsible for mental illness has resulted in different approaches to surmount this obstacle.
Bi-Frontal Stereotactic Tractotomy
Authors: Ström-Olsen Rolf , Carlisle Sheila
Published: August 2008

Since 1955 there has been a steady decline in the number of leucotomy operations, particularly of the open standard type introduced into this country in 1941. It has been considered by most authors that the undesirable side-effects caused this decline but no doubt the introduction of ataractic drugs also played its part (Pippard, 1962). Sykes and Tredgold (1964) discussed in detail the literature up to that time and it was felt unnecessary to repeat that survey here. Suffice it to say that from about 1949 various modifications of the standard operation were devised in the hope of diminishing or eliminating undesirable sequelae. Following the publication of a paper on the late social results of pre-frontal leucotomy by Ström-Olsen and Tow (1949) the late Alexander Kennedy (1949) wrote in the correspondence column of theLancet—‘The future of this kind of operation (i.e. standard leucotomy) lies in limited and accurately localized sections. The correlation of these with their clinical and neuropathological effects offers a field of study which will occupy us for many years to come’.
Classification of Depressed Patients: A Cluster Analysis Derived Grouping
Authors: Paykel E. S.
Published: August 2008

In recent years there has been a considerable interest in the classification of depressed patients, and in the use of multivariate statistical techniques as tools for classifying, with the hope of either validating traditional classifications or suggesting useful new ones. One technique employed for this purpose has been factor analysis. A number of studies have used this method to explore the overlapping endogenous-reactive or psychotic-neurotic dichotomies. Most have demonstrated a factor or factors reflecting such a dimension which appears to form a consistent, systematic source of variance in ratings of depressed patients (1, 5, 11, 15, 16, 18, 26, 31, 33).
Depression and Attempted Suicide: A Study of 91 Cases Seen in a Casualty Department
Authors: Birtchnell John , Alarcon José
Published: August 2008

In recent years there has been a steady and alarming increase in the prevalence of attempted suicide (Aitken, Buglass and Kreitman, 1969). Though all cases of attempted suicide may be regarded as a distress signal, only a proportion of such cases are seriously mentally ill. The problem of their assessment and organization of appropriate treatment is becoming an increasing burden on the psychiatric services. The Hill Report (1968) recommended that all cases should be admitted to special poisoning treatment centres which have continuous psychiatric cover. In towns where there are medical schools this may be a feasible proposition, and such a centre has been in operation in Edinburgh for a number of years (Matthew, Proudfoot, Brown and Aitken, 1969). In the Aberdeen region all cases are treated in the city casualty department and are assessed by the staff of the Professorial Psychiatric Unit, which is less than a mile away. Seven day cover is provided by a duty rota, each doctor being on call for a period of twenty-four hours. In a non-university town with less staff available such an efficient service may not be possible, and Crammer (1969) has suggested that a questionary administered by the house officer in the casualty department might serve as a satisfactory screening procedure.
Schizophrenia and XO/XX/XXX Mosaicism
Authors: Beumont P. J. V. , Mayou Richard
Published: August 2008

Abnormalities of sex chromosomes are associated with various forms of neuropsychiatric disorder, and Polani (1969) has reviewed the literature. While there were numerous reports associating the XXY and XXX constitutions with psychiatric disorder, the position was somewhat different with regard to Turner's syndrome. The purpose of this paper is to describe a patient who was shown to have the clinical pattern of Turner's Syndrome and an XO/XX/XXX mosaic chromosome pattern, and who presented with a schizophrenic illness.
V. Cerebral Dysfunction and Childhood Psychoses
Authors: Kolvin I. , Ounsted C. , Roth M.
Published: August 2008

A series of recent papers (Creak, 1961, 1963; Rutter, 1966; Brown, 1963; Lotter, 1967; Schain and Yannet, 1960) have provided evidence of degrees of cerebral dysfunction in infantile autism (Kanner, 1943) and other infantile psychoses. They have demonstrated that groups of cases of infantile psychoses satisfying broadly similar diagnostic criteria have in their backgrounds a variable frequency of cerebral insult and abnormal discharge in the EEC The diagnostic criteria in such series are of crucial importance. Imprecision and vagueness hamper comparisons between series. In childhood psychoses some investigators have excluded those cases in which there was any history or clinical evidence of organic features in an attempt to obtain a ‘pure’ group. This technique, while valid in delineating a syndrome, is handicapping to subsequent etiological study. For these reasons the present authors have used only age of onset and behavioural features as their ascertainment criteria it was a behavioural rather than an aetiological diagnosis.
The Response of Chronic Schizophrenics to Attention and Structure
Authors: Ludwig Arnold M. , Marx Arnold J.
Published: August 2008

There have been numerous psychotherapeutic approaches (e.g., total push, community therapy, token economy, buddy system, etc.) advocated for hospitalized chronic schizophrenics. Although these programs have had relative success in producing improvement in at least some of these patients, it remains to be demonstrated whether this improvement is due to the specific nature of these programs or to certain non-specific factors, such as attention and/or structure, common to all psychotherapeutic interactions.
Birth Weight and Length in Schizophrenics Personality Disorders and Their Siblings
Authors: Woerner Margaret G. , Pollack Max , Klein Donald F.
Published: August 2008

Evidence from a detailed investigation and review of the literature on monozygotic twins discordant for schizophrenia indicates that the schizophrenic index case was lighter in weight at birth than his co-twin (Stabenau and Pollin, 1967). Lane and Albee (1966) reported that schizophrenic singletons were significantly lighter in birth weight than their sibs.
Decarboxylation of Radioactive DOPA by Erythrocytes in Schizophrenia
Authors: Tran Ngo , Laplante Marcel , Lebel Etienne
Published: August 2008

The decarboxylation of 3, 4-dihydroxyphenyl-alanine (Dopa) to dopamine has been shown previously in animal and human tissues in bothin vitroandin vivostudies (Sourkes, 1966; Vogelet al., 1970). However, very little information is available as to whether or not the decarboxylation of Dopa occurs in human red blood cells (RBC). In the present experiment we demonstrated this change in RBC from normals and from schizophrenics. An ionization chamber method was used for an instantaneous and continuous measurement of14CO2production from DL-dopa-carboxyl-14C by RBCin vitro.
Mental Health in an Indian Rural Community
Authors: Elnagar M. N. , Maitra Promila , Rao M. N.
Published: August 2008

The difficulties of organizing mental health services in developing countries are made all the greater by inadequacy of information about the extent of illness and disability. Some beginnings have been made in India, particularly under the sponsorship of the All India Institute of Mental Health, Bangalore. The Mental Health Advisory Committee of the Government of India (1966) suggested a probable prevalence of mental illness of 20 per 1,000 population in general, 18 per mille for semi-rural and 14 per mille for rural areas. These figures are much lower than the 72 per 1,000 suggested by Sethi et al. (1967). Ganguli (1968) estimated a prevalence rate of 140 per 1,000 in industrial workers near Delhi. Incidence rates have been much less studied than prevalences (Lin and Standley, 1962). A WHO Expert Committee on mental health convened in 1960 suggested as a working definition of a case of mental illness:
Alcoholism IV: is There More Than One Type of Alcoholism?
Authors: Winokur George , Rimmer John , Reich Theodore
Published: August 2008

In a previous study we presented preliminary evidence indicating that there may be two types of alcoholism in women (Schuckit, Pitts, Reich, King and Winokur, 1969). These types were called primary alcoholism and affective-disorder-alcoholism. The affective-disorder-alcoholic woman showed evidence that she had had a clear-cut affective episode which was either independent of the alcoholic intake or had occurred prior to the time alcohol had become a problem. Suicide attempts were significantly more frequently seen among the affective-disorder-alcoholic women than among the primary alcoholic women. As regards the family history there was significantly more affective disorder in the families of affective-disorder-alcoholic women than in those of the primary alcoholics. It appeared, then, that there were two types of alcoholism among women hospitalized for alcoholic abuse.