bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors
Authors: Voisin Laure , Julien Catherine , Duhamel Stéphanie , Gopalbhai Kailesh , Claveau Isabelle , Saba-El-Leil Marc K , Rodrigue-Gervais Ian Gaël , Gaboury Louis , Lamarre Daniel , Basik Mark , Meloche Sylvain
Published: November 2008

Background

The Ras-dependent ERK1/2 MAP kinase signaling pathway plays a central role in cell proliferation control and is frequently activated in human colorectal cancer. Small-molecule inhibitors of MEK1/MEK2 are therefore viewed as attractive drug candidates for the targeted therapy of this malignancy. However, the exact contribution of MEK1 and MEK2 to the pathogenesis of colorectal cancer remains to be established.

Methods

Wild type and constitutively active forms of MEK1 and MEK2 were ectopically expressed by retroviral gene transfer in the normal intestinal epithelial cell line IEC-6. We studied the impact of MEK1 and MEK2 activation on cellular morphology, cell proliferation, survival, migration, invasiveness, and tumorigenesis in mice. RNA interference was used to test the requirement for MEK1 and MEK2 function in maintaining the proliferation of human colorectal cancer cells.

Results

We found that expression of activated MEK1 or MEK2 is sufficient to morphologically transform intestinal epithelial cells, dysregulate cell proliferation and induce the formation of high-grade adenocarcinomas after orthotopic transplantation in mice. A large proportion of these intestinal tumors metastasize to the liver and lung. Mechanistically, activation of MEK1 or MEK2 up-regulates the expression of matrix metalloproteinases, promotes invasiveness and protects cells from undergoing anoikis. Importantly, we show that silencing of MEK2 expression completely suppresses the proliferation of human colon carcinoma cell lines, whereas inactivation of MEK1 has a much weaker effect.

Conclusion

MEK1 and MEK2 isoforms have similar transforming properties and are able to induce the formation of metastatic intestinal tumors in mice. Our results suggest that MEK2 plays a more important role than MEK1 in sustaining the proliferation of human colorectal cancer cells.
Prompt letters to reduce non-attendance: applying evidence based practice
Authors: Jayaram Mahesh , Rattehalli Ranganath D , Kader Ihsan
Published: November 2008

Background

Non-attendance rates in psychiatric outpatient clinics have been a topic of considerable interest. It is measured as an indicator of quality of service provision. Failed attendances add to the cost of care as well as having an adverse impact on patients leading to missing medications, delay in identifying relapses and increasing waiting list time. Recent trials have demonstrated that prompting letters sent to patients led to a decrease in non-attendance rates. We applied this evidence based practice in our community mental health setting to evaluate its impact.

Methods

Using a before and after study design, we sent prompting letters to all patients due to attend outpatient clinic appointments for a period of six months in 2007. Non-attendance rates were compared with the corresponding period in 2006. We also looked at trends of non-attendance prior to this intervention and compared results with other parts of our service where this intervention had not been applied.

Results

1433 prompting letters were sent out to all out-patient appointments made from June to November 2007. This resulted in an average non-attendance rate of 17% which was significantly less compared to 27% between June and November 2006 (RR 0.65, 95% CI 0.56 to 0.76, NNT 11). No downward trend in non-attendance rate was identified either prior to the intervention or when compared with similar teams across the city.

Conclusion

Prompt letters have been shown to reduce non-attendance rates in previous RCTs and systematic reviews. Our findings demonstrate a reduction in non-attendance rates with prompting letters even under non-trial conditions. Majority of the patients were constant during the two periods compared although there were some changes in medical personnel. This makes it difficult to attribute all the change, solely to the intervention alone. Perhaps our work shows that the results of pragmatic randomised trials are easily applicable and produce similar results in non-randomised settings. We found that prompting letters are a useful and easy to apply evidence based intervention to reduce non-attendance rates with a potential to achieve significant cost savings.
Enzyme controlled glucose auto-delivery for high cell density cultivations in microplates and shake flasks
Authors: Panula-Perälä Johanna , Šiurkus Juozas , Vasala Antti , Wilmanowski Robert , Casteleijn Marco G , Neubauer Peter
Published: November 2008

Background

Here we describe a novel cultivation method, called EnBase™, or enzyme-based-substrate-delivery, for the growth of microorganisms in millilitre and sub-millilitre scale which yields 5 to 20 times higher cell densities compared to standard methods. The novel method can be directly applied in microwell plates and shake flasks without any requirements for additional sensors or liquid supply systems. EnBase is therefore readily applicable for many high throughput applications, such as DNA production for genome sequencing, optimisation of protein expression, production of proteins for structural genomics, bioprocess development, and screening of enzyme and metagenomic libraries.

Results

High cell densities with EnBase are obtained by applying the concept of glucose-limited fed-batch cultivation which is commonly used in industrial processes. The major difference of the novel method is that no external glucose feed is required, but glucose is released into the growth medium by enzymatic degradation of starch. To cope with the high levels of starch necessary for high cell density cultivation, starch is supplied to the growing culture suspension by continuous diffusion from a storage gel.

Our results show that the controlled enzyme-based supply of glucose allows a glucose-limited growth to high cell densities of OD600 = 20 to 30 (corresponding to 6 to 9 g l-1 cell dry weight) without the external feed of additional compounds in shake flasks and 96-well plates. The final cell density can be further increased by addition of extra nitrogen during the cultivation. Production of a heterologous triosphosphate isomerase in E. coli BL21(DE3) resulted in 10 times higher volumetric product yield and a higher ratio of soluble to insoluble product when compared to the conventional production method.

Conclusion

The novel EnBase method is robust and simple-to-apply for high cell density cultivation in shake flasks and microwell plates. The potential of the system is that the microbial growth rate and oxygen consumption can be simply controlled by the amount (and principally also by the activity) of the starch-degrading enzyme. This solves the problems of uncontrolled growth, oxygen limitation, and severe pH drop in shaken cultures. In parallel the method provides the basis for enhanced cell densities. The feasibility of the new method has been shown for 96-well plates and shake flasks and we believe that it can easily be adapted to different microwell and deepwell plate formats and shake flasks. Therefore EnBase will be a helpful tool especially in high throughput applications.
Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells
Authors: Hurtubise Annie , Bernstein Mark L , Momparler Richard L
Published: November 2008

Background

Most patients with advanced Ewing's sarcoma (EWS) respond poorly to conventional chemotherapy, indicating the need for new treatment approaches. Epigenetic events, such as promoter hypermethylation and chromatin histone deacetylation, silence the expression of tumor suppressor genes (TSGs) and play an important role in tumorigenesis. These epigenetic changes can be reversed by using 5-aza-2'-deoxycytidine (5AZA-CdR), a potent inhibitor of DNA methylation, in combination with an inhibitor of histone deacetylase (HDAC).

Results

Here, we used a clonogenic assay to evaluate the in vitro antineoplastic activity of 5AZA-CdR in combination with different HDAC inhibitors on EWS cells. We observed that the HDAC inhibitors, MS-275, trichostatin-A, phenylbutyrate, LAQ824 and depsipeptide, enhanced the antineoplastic action of 5AZA-CdR on EWS cells. The combination of 5AZA-CdR and MS-275 showed marked synergy, and was correlated with significant reactivation of the expression of two TSGs, E-cadherin and tumor suppressor lung cancer-1 (TSLC1), in a EWS cell line.

Conclusion

These results suggest the value of future clinical studies investigating the combination of 5AZA-CdR and MS-275 in patients with advanced EWS.
Left atrioventricular remodeling in the assessment of the left ventricle diastolic function in patients with heart failure: a review of the currently studied echocardiographic variables
Authors: Danzmann Luiz C , Bodanese Luiz Carlos , Köhler Ilmar , Torres Marco R
Published: November 2008

Multiparametric echocardiographic imaging of the failing heart is now increasingly used and useful in decision making in heart failure. The reasons for this, relies on the need of different strategies of handling these patients, as differentiation of systolic or diastolic dysfunction, as well as on the gamma of approaches available, such as percutaneous and surgical revascularization, devices implantations, and valvular regurgitations and stenosis corrections. Congestive heart failure in patients with normal left ventricular diameters or preserved left ventricular ejection fraction had been pointed out recently as present in a proportion so high as 40 to 50 percent of cases of heart failure, mainly due to the epidemics in well developed countries, as is the problem of not well controlled metabolic states (such as obesity and diabetes), but also due to the real word in developing countries, as is the case of hypertension epidemics and its lack of adequate control. As a matter of public utility, the guidelines in the diagnosis and treatment of such patients will have to be cheap, available, easily reproducible, and ideally will furnish answers for the clinician questions not in a binary "black or white" manner, but with graduations, so if possible it has to be quantitative. The present paper aim to focus on the current clinical applications of tissue Doppler and of left atrial function and remodeling, and its pathophysiologic relationship with the left ventricle, as will be cleared in the documented review of echocardiography that follows, considering that the need of universal data on the syndrome of the failing heart does not mean, unfortunately, that all patients and clinicians in developing countries have at their own health facilities the same imaging tools, since they are, as a general rule, expensive.
Lack of association between sCTLA-4 levels in human plasma and common CTLA-4 polymorphisms
Authors: Berry Andrew , Tector Matt , Oaks Martin K
Published: November 2008

Background

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an important downregulatory molecule expressed on both T and B lymphocytes. Numerous population genetics studies have documented significant associations between autoimmune diseases and single nucleotide polymorphisms (SNPs) within and around the CTLA-4 region of chromosome 2 in man. Furthermore, circulating levels of a soluble form of CTLA-4 (sCTLA-4) have been reported in a variety of autoimmune mediated diseases. Despite these findings, the relationship between levels of sCTLA-4 protein, mRNA transcript levels, and SNPs within the CTLA-4 region have not been clearly defined. In order to further clarify this relationship, we have tested four different SNPs within the CTLA-4 region among subjects whom are negative (n = 53) versus positive (n = 28) for sCTLA-4.

Results

Our data do not support a clear association between sCTLA-4 levels and any of the four SNPs tested.

Conclusion

The variation in the SNPs tested does not appear to effect sCTLA-4 protein levels, despite reports that they affect sCTLA-4 mRNA.
Toll-like receptor and antimicrobial peptide expression in the bovine endometrium
Authors: Davies Darren , Meade Kieran G , Herath Shan , Eckersall P David , Gonzalez Deyarina , White John O , Conlan R Steven , O'Farrelly Cliona , Sheldon I Martin
Published: November 2008

Background

The endometrium is commonly infected with bacteria leading to severe disease of the uterus in cattle and humans. The endometrial epithelium is the first line of defence for this mucosal surface against bacteria and Toll-like receptors (TLRs) are a critical component of the innate immune system for detection of pathogen associated molecular patterns (PAMPs). Antimicrobial peptides, acute phase proteins and Mucin-1 (MUC-1) also provide non-specific defences against microbes on mucosal surfaces. The present study examined the expression of innate immune defences in the bovine endometrium and tested the hypothesis that endometrial epithelial cells express functional receptors of the TLR family and the non-specific effector molecules for defence against bacteria.

Methods

Bovine endometrial tissue and purified populations of primary epithelial and stromal cells were examined using RT-PCR for gene expression of TLRs, antimicrobial peptides and MUC-1. Functional responses were tested by evaluating the secretion of prostaglandin E2 and acute phase proteins when cells were treated with bacterial PAMPs such as bacterial lipopolysaccharide (LPS) and lipoproteins.

Results

The endometrium expressed TLRs 1 to 10, whilst purified populations of epithelial cells expressed TLRs 1 to 7 and 9, and stromal cells expressed TLRs 1 to 4, 6, 7, 9 and 10. The TLRs appear to be functional as epithelial cells secreted prostaglandin E2 in response to bacterial PAMPs. In addition, the epithelial cells expressed antimicrobial peptides, such as Tracheal and Lingual Antimicrobial Peptides (TAP and LAP) and MUC-1, which were upregulated when the cells were treated with LPS. However, the epithelial cells did not express appreciable amounts of the acute phase proteins haptoglobin or serum amyloid A.

Conclusion

Epithelial cells have an essential role in the orchestration of innate immune defence of the bovine endometrium and are likely to be the key to prevention of endometrial infection with bacteria.
Cost-effectiveness analysis for joint pain treatment in patients with osteoarthritis treated at the Instituto Mexicano del Seguro Social (IMSS): Comparison of nonsteroidal anti-inflammatory drugs (NSAIDs) vs. cyclooxygenase-2 selective inhibitors
Authors: Contreras-Hernández Iris , Mould-Quevedo Joaquín F , Torres-González Rubén , Goycochea-Robles María Victoria , Pacheco-Domínguez Reyna Lizette , Sánchez-García Sergio , Mejía-Aranguré Juan Manuel , Garduño-Espinosa Juan
Published: November 2008

Background

Osteoarthritis (OA) is one of the main causes of disability worldwide, especially in persons >55 years of age. Currently, controversy remains about the best therapeutic alternative for this disease when evaluated from a cost-effectiveness viewpoint. For Social Security Institutions in developing countries, it is very important to assess what drugs may decrease the subsequent use of medical care resources, considering their adverse events that are known to have a significant increase in medical care costs of patients with OA. Three treatment alternatives were compared: celecoxib (200 mg twice daily), non-selective NSAIDs (naproxen, 500 mg twice daily; diclofenac, 100 mg twice daily; and piroxicam, 20 mg/day) and acetaminophen, 1000 mg twice daily. The aim of this study was to identify the most cost-effective first-choice pharmacological treatment for the control of joint pain secondary to OA in patients treated at the Instituto Mexicano del Seguro Social (IMSS).

Methods

A cost-effectiveness assessment was carried out. A systematic review of the literature was performed to obtain transition probabilities. In order to evaluate analysis robustness, one-way and probabilistic sensitivity analyses were conducted. Estimations were done for a 6-month period.

Results

Treatment demonstrating the best cost-effectiveness results [lowest cost-effectiveness ratio $17.5 pesos/patient ($1.75 USD)] was celecoxib. According to the one-way sensitivity analysis, celecoxib would need to markedly decrease its effectiveness in order for it to not be the optimal treatment option. In the probabilistic analysis, both in the construction of the acceptability curves and in the estimation of net economic benefits, the most cost-effective option was celecoxib.

Conclusion

From a Mexican institutional perspective and probably in other Social Security Institutions in similar developing countries, the most cost-effective option for treatment of knee and/or hip OA would be celecoxib.
Age-related appearance of a CMV-specific high-avidity CD8+ T cell clonotype which does not occur in young adults
Authors: Schwanninger Angelika , Weinberger Birgit , Weiskopf Daniela , Herndler-Brandstetter Dietmar , Reitinger Stephan , Gassner Christoph , Schennach Harald , Parson Walther , Würzner Reinhard , Grubeck-Loebenstein Beatrix
Published: November 2008

Old age is associated with characteristic changes of the immune system contributing to higher incidence and severity of many infectious diseases. Particularly within the T cell compartment latent infection with human Cytomegalovirus (CMV) is contributing to and accelerating immunosenescence. However, latent CMV infection and reactivation usually does not cause overt symptoms in immunocompetent elderly persons indicating immunological control of disease. Little is still known about the clonal composition of CMV-specific T cell responses in donors of different age. We therefore analyzed CD8+T cells specific for an immunodominant pp65-derived nonamer-peptide (NLVPMVATV; CMVNLV) in different age-groups. Independent of donor age CMVNLV-specific CD8+T cells preferentially use the V beta family 8. This family has monoclonal expansions in the majority of donors after stimulation of CD8+T cells with the peptide. By sequencing the CDR3 region of the T cell receptor we demonstrated that CMVNLV-specific, BV8+CD8+T cells share the conserved CDR3-sequence motif SANYGYT in donors of all age groups. Interestingly, a second conserved clonotype with the CDR3-sequence motif SVNEAF appears in middle-aged and elderly donors. This clonotype is absent in young individuals. The age-related clonotype SVNEAF binds to the pMHC-complex with higher avidity than the clonotype SANYGYT, which is predominant in young adults. The dominance of this high avidity clonotype may explain the lack of overt CMV-disease in old age.
Development of a quality assessment tool for systematic reviews of observational studies (QATSO) of HIV prevalence in men having sex with men and associated risk behaviours
Authors: Wong William CW , Cheung Catherine SK , Hart Graham J
Published: November 2008

Background

Systematic reviews based on the critical appraisal of observational and analytic studies on HIV prevalence and risk factors for HIV transmission among men having sex with men are very useful for health care decisions and planning. Such appraisal is particularly difficult, however, as the quality assessment tools available for use with observational and analytic studies are poorly established.

Methods

We reviewed the existing quality assessment tools for systematic reviews of observational studies and developed a concise quality assessment checklist to help standardise decisions regarding the quality of studies, with careful consideration of issues such as external and internal validity.

Results

A pilot version of the checklist was developed based on epidemiological principles, reviews of study designs, and existing checklists for the assessment of observational studies. The Quality Assessment Tool for Systematic Reviews of Observational Studies (QATSO) Score consists of five items: External validity (1 item), reporting (2 items), bias (1 item) and confounding factors (1 item). Expert opinions were sought and it was tested on manuscripts that fulfil the inclusion criteria of a systematic review. Like all assessment scales, QATSO may oversimplify and generalise information yet it is inclusive, simple and practical to use, and allows comparability between papers.

Conclusion

A specific tool that allows researchers to appraise and guide study quality of observational studies is developed and can be modified for similar studies in the future.
Age-related differences in dual task walking: a cross sectional study
Authors: Priest Andrew W , Salamon Kathleen B , Hollman John H
Published: November 2008

Background

Variability in stride velocity during walking characterizes gait instability and predicts falling in older individuals. Walking while executing a cognitive task is also associated with increased risk of falling, particularly in older adults. Variability in stride velocity, particularly during dual task walking conditions, may differ between younger and older individuals. The purpose of this study was to examine whether gait velocity and variability in stride velocity differ between older community-dwelling women and younger women during dual task walking.

Methods

Twenty-three older (80 ± 9 years) and 19 younger (23 ± 2 years) women walked under each of two conditions: (1) walking at a self-selected velocity and (2) walking at a self-selected velocity while incrementally counting backwards. Gait velocity and variability in stride velocity were measured with GAITRite® instrumentation.

Results

Gait velocity decreased and variability in stride variability increased, in both groups, during dual task walking. The relative reduction in gait velocity and the magnitude of variability in stride velocity were greater in the older subjects than younger subjects.

Conclusion

The gait changes observed in dual task walking characterize reduced gait stability and indicate that cognitively demanding tasks during walking have a destabilizing effect on gait that may place older persons at greater risk of falls.
Field evaluation of a new particle concentrator- electrostatic precipitator system for measuring chemical and toxicological properties of particulate matter
Authors: Ning Zhi , Sillanpää Markus , Pakbin Payam , Sioutas Constantinos
Published: November 2008

Background

A newly designed electrostatic precipitator (ESP) in tandem with Versatile Aerosol Concentration Enrichment System (VACES) was developed by the University of Southern California to collect ambient aerosols on substrates appropriate for chemical and toxicological analysis. The laboratory evaluation of this sampler is described in a previous paper. The main objective of this study was to evaluate the performance of the new VACES-ESP system in the field by comparing the chemical characteristics of the PM collected in the ESP to those of reference samplers operating in parallel.

Results

The field campaign was carried out in the period from August, 2007 to March, 2008 in a typical urban environment near downtown Los Angeles. Each sampling set was restricted to 2–3 hours to minimize possible sampling artifacts in the ESP. The results showed that particle penetration increases and ozone concentration decreases with increasing sampling flow rate, with highest particle penetration observed between 100 nm and 300 nm. A reference filter sampler was deployed in parallel to the ESP to collect concentration-enriched aerosols, and a MOUDI sampler was used to collect ambient aerosols. Chemical analysis results showed very good agreement between the ESP and MOUDI samplers in the concentrations of trace elements and inorganic ions. The overall organic compound content of PM collected by the ESP, including polycyclic aromatic hydrocarbons (PAHs), hopanes, steranes, and alkanes, was in good agreement with that of the reference sampler, with an average ESP -to -reference concentration ratio of 1.07 (± 0.38). While majority of organic compound ratios were close to 1, some of the semi-volatile organic species had slightly deviated ratios from 1, indicating the possibility of some sampling artifacts in the ESP due to reactions of PM with ozone and radicals generated from corona discharge, although positive and negative sampling artifacts in the reference filter sampler cannot be ruled out.

Conclusion

The very good overall agreement between ESP and reference samplers makes it an attractive alternative to filters and biosamplers for chemical and toxicological evaluation of PM properties, including the possibility of conducting direct in vitro cell exposures. Moreover, the concentration enrichment of ambient aerosols by the VACES allows for short-term exposure studies, which preserve cell viability and enable studies to PM generated from specific sources and-or formation mechanisms in the atmosphere.
Autonomic Fiber Sprouting in the Skin in Chronic Inflammation
Authors: Almarestani Lina , Longo Geraldine , Ribeiro-da-Silva Alfredo
Published: November 2008

Pain is a major symptom associated with chronic inflammation. In previous work from our laboratory, we have shown that in animal models of neuropathic pain there is a sprouting of sympathetic fibers into the upper dermis, a territory normally devoid of them. However, it is not known whether such sympathetic spouting, which is likely trophic factor mediated, also occurs in chronic inflammation and arthritis. In the present study, we used a rat model of chronic inflammation in which a small single dose of complete Freund's adjuvant (CFA) was injected subcutaneously, unilaterally, into the plantar surface of the hindpaw. This led to a localized long-term skin inflammation and arthritis in all joints of the hindpaw. Animals were perfused with histological fixatives at 1, 2, 3 or 4 weeks after the injection. Experimental animals treated with CFA were compared to saline-injected animals. We then investigated the changes in the pattern of peripheral innervation of the peptidergic nociceptors and sympathetic fibers in rat glabrous hindpaw skin. Antibodies directed towards calcitonin gene-related peptide (CGRP) and dopamine beta-hydroxylase (DBH) were used for the staining of peptidergic and sympathetic fibers, respectively. Immunofluorescence was then used to analyze the different nerve fiber populations of the upper dermis. At 4 weeks following CFA treatment, DBH-immunoreactive (IR) fibers were found to sprout into the upper dermis, in a pattern similar to the one we had observed in animals with a chronic constriction injury of the sciatic nerve in a previous publication. There was also a significant increase in the density of CGRP-IR fibers in the upper dermis in CFA treated animals at 2, 3 and 4 weeks post-injection. The increased peptidergic fiber innervation and the ectopic autonomic fibers found in the upper dermis may have a role in the pain-related behavior displayed by these animals.
The clinical-familial correlates and naturalistic outcome of panic-disorder-agoraphobia with and without lifetime bipolar II comorbidity
Authors: Toni Cristina , Perugi Giulio , Frare Franco , Tusini Giuseppe , Fountoulakis Konstantinos N , Akiskal Kareen K , Akiskal Hagop S
Published: November 2008

Background

Much of the literature on panic disorder (PD)-bipolar disorder (BP) cormorbidity concerns BP-I. This literature emphasizes the difficulties encountered in pharmacologic treatment and outcome when such comorbidity is present. The present report explores these issues with respect to BP-II.

Methods

The sample comprised 326 outpatients (aged 34.5 ± 11.5 years old; 222 females) with Diagnostic and Statistical Manual of Mental Disorders 3rd edn, revised (DSM-III-R) PD-agoraphobia; among them 52 subjects (16%) were affected by lifetime comorbidity with BP-II. Patients were evaluated by means of the Structured Clinical Interview for DSM-IV (SCID), the Panic-Agoraphobia Interview, and the Longitudinal Interview Follow-up Examination (Life-Up) and treated according to routine clinical practice at the University of Pisa, Italy, for a period of 3 years. Clinical and course features were compared between subjects with and without BP-II. All patients received the clinicians' choice of antidepressants and, in the case of the subsample with BP-II, mood stabilizers (for example, valproate, lithium) were among the mainstays of treatment.

Results

In comparison to patients without bipolar comorbidity, those with BP-II showed a significantly greater frequency of social phobia, obsessive-compulsive disorder, alcohol-related disorders, and separation anxiety during childhood and adolescence. Regarding family history, a significantly greater frequency of PD and mood disorders was present among the BP-II. No significant differences were observed in the long-term course of PD or agoraphobic symptoms under pharmacological treatment or the likelihood of spontaneous pharmacological treatment interruptions.

Conclusion

Although the severity and outcome of panic-agoraphobic symptomatology appear to be similar in patients with and without lifetime bipolar comorbidity, the higher number of concomitant disorders in our PD patients with BP-II does indicate a greater complexity of the clinical picture in this naturalistic study. That such complexity does not seem to translate into poorer response and outcome in those with comorbid soft bipolarity probably reflects the fact that we had brought BP-II under control with mood stabilizers. We discuss the implications of our findings as further evidence for the existence of a distinct anxious-bipolar diathesis.
Molecular characterisation of a bovine-like rotavirus detected from a giraffe
Authors: Mulherin Emily , Bryan Jill , Beltman Marijke , O'Grady Luke , Pidgeon Eugene , Garon Lucie , Lloyd Andrew , Bainbridge John , O'Shea Helen , Whyte Paul , Fanning Séamus
Published: November 2008

Background

Rotavirus (RV), is a member of the Reoviridae family and an important etiological agent of acute viral gastroenteritis in the young. Rotaviruses have a wide host range infecting a broad range of animal species, however little is known about rotavirus infection in exotic animals. In this paper we report the first characterisation of a RV strain from a giraffe calf.

Results

This report describes the identification and detailed molecular characterisation of a rotavirus strain detected from a 14-day-old Giraffe (Giraffa camelopardalis), presenting with acute diarrhea. The RV strain detected from the giraffe was characterized molecularly as G10P[11]. Detailed sequence analysis of VP4 and VP7 revealed significant identity at the amino acid sequence level to Bovine RV (BoRV).

Conclusion

This study demonstrates the need for continuous surveillance of RV strains in various animal populations, which will facilitate the identification of rotavirus hosts not previously reported. Furthermore, extending typical epidemiology studies to a broader host range will contribute to the timely identification of new emerging strain types.
Panic disorder and locomotor activity
Authors: Sakamoto Noriyuki , Yoshiuchi Kazuhiro , Kikuchi Hiroe , Takimoto Yoshiyuki , Kaiya Hisanobu , Kumano Hiroaki , Yamamoto Yoshiharu , Akabayashi Akira
Published: November 2008

Background

Panic disorder is one of the anxiety disorders, and anxiety is associated with some locomotor activity changes such as "restlessness". However, there have been few studies on locomotor activity in panic disorder using actigraphy, although many studies on other psychiatric disorders have been reported using actigraphy. Therefore, the aim of the present study was to investigate the relationship between panic disorder and locomotor activity pattern using a wrist-worn activity monitor. In addition, an ecological momentary assessment technique was used to record panic attacks in natural settings.

Methods

Sixteen patients with panic disorder were asked to wear a watch-type computer as an electronic diary for recording panic attacks for two weeks. In addition, locomotor activity was measured and recorded continuously in an accelerometer equipped in the watch-type computer. Locomotor activity data were analyzed using double cosinor analysis to calculate mesor and the amplitude and acrophase of each of the circadian rhythm and 12-hour harmonic component. Correlations between panic disorder symptoms and locomotor activity were investigated.

Results

There were significant positive correlations between the frequency of panic attacks and mesor calculated from double cosinor analysis of locomotor activity (r = 0.55) and between HAM-A scores and mesor calculated from double cosinor analysis of locomotor activity (r = 0.62).

Conclusion

Panic disorder patients with more panic attacks and more anxiety have greater objectively assessed locomotor activity, which may reflect the "restlessness" of anxiety disorders.
Searching for molecular markers in head and neck squamous cell carcinomas (HNSCC) by statistical and bioinformatic analysis of larynx-derived SAGE libraries
Authors: Silveira Nelson JF , Varuzza Leonardo , Machado-Lima Ariane , Lauretto Marcelo S , Pinheiro Daniel G , Rodrigues Rodrigo V , Severino Patrícia , Nobrega Francisco G ,   Head and Neck Genome Project GENCAPO, Silva Wilson A , de B Pereira Carlos A , Tajara Eloiza H
Published: November 2008

Background

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies in humans. The average 5-year survival rate is one of the lowest among aggressive cancers, showing no significant improvement in recent years. When detected early, HNSCC has a good prognosis, but most patients present metastatic disease at the time of diagnosis, which significantly reduces survival rate. Despite extensive research, no molecular markers are currently available for diagnostic or prognostic purposes.

Methods

Aiming to identify differentially-expressed genes involved in laryngeal squamous cell carcinoma (LSCC) development and progression, we generated individual Serial Analysis of Gene Expression (SAGE) libraries from a metastatic and non-metastatic larynx carcinoma, as well as from a normal larynx mucosa sample. Approximately 54,000 unique tags were sequenced in three libraries.

Results

Statistical data analysis identified a subset of 1,216 differentially expressed tags between tumor and normal libraries, and 894 differentially expressed tags between metastatic and non-metastatic carcinomas. Three genes displaying differential regulation, one down-regulated (KRT31) and two up-regulated (BST2,MFAP2), as well as one with a non-significant differential expression pattern (GNA15) in our SAGE data were selected for real-time polymerase chain reaction (PCR) in a set of HNSCC samples. Consistent with our statistical analysis, quantitative PCR confirmed the upregulation ofBST2andMFAP2and the downregulation ofKRT31when samples of HNSCC were compared to tumor-free surgical margins. As expected,GNA15presented a non-significant differential expression pattern when tumor samples were compared to normal tissues.

Conclusion

To the best of our knowledge, this is the first study reporting SAGE data in head and neck squamous cell tumors. Statistical analysis was effective in identifying differentially expressed genes reportedly involved in cancer development. The differential expression of a subset of genes was confirmed in additional larynx carcinoma samples and in carcinomas from a distinct head and neck subsite. This result suggests the existence of potential common biomarkers for prognosis and targeted-therapy development in this heterogeneous type of tumor.
Multivariate profiling of neurodegeneration-associated changes in a subcellular compartment of neurons via image processing
Authors: Kumarasamy Saravana K , Wang Yunshi , Viswanathan Vignesh , Kraut Rachel S
Published: November 2008

Background

Dysfunction in the endolysosome, a late endosomal to lysosomal degradative intracellular compartment, is an early hallmark of some neurodegenerative diseases, in particular Alzheimer's disease. However, the subtle morphological changes in compartments of affected neurons are difficult to quantify quickly and reliably, making this phenotype inaccessible as either an early diagnostic marker, or as a read-out for drug screening.

Methods

We present a method for automatic detection of fluorescently labeled endolysosomes in degenerative neurons in situ. The Drosophila blue cheese (bchs) mutant was taken as a genetic neurodegenerative model for direct in situ visualization and quantification of endolysosomal compartments in affected neurons. Endolysosomal compartments were first detected automatically from 2-D image sections using a combination of point-wise multi-scale correlation and normalized correlation operations. This detection algorithm performed well at recognizing fluorescent endolysosomes, unlike conventional convolution methods, which are confounded by variable intensity levels and background noise. Morphological feature differences between endolysosomes from wild type vs. degenerative neurons were then quantified by multivariate profiling and support vector machine (SVM) classification based on compartment density, size and contrast distribution. Finally, we ranked these distributions according to their profiling accuracy, based on the backward elimination method.

Results

This analysis revealed a statistically significant difference between the neurodegenerative phenotype and the wild type up to a 99.9% confidence interval. Differences between the wild type and phenotypes resulting from overexpression of the Bchs protein are detectable by contrast variations, whereas both size and contrast variations distinguish the wild type from either of the loss of function alleles bchs1 or bchs58. In contrast, the density measurement differentiates all three bchs phenotypes (loss of function as well as overexpression) from the wild type.

Conclusion

Our model demonstrates that neurodegeneration-associated endolysosomal defects can be detected, analyzed, and classified rapidly and accurately as a diagnostic imaging-based screening tool.
Catheter-related septic thrombophlebitis of the superior vena cava involving the atrial septum: a case report
Authors: Tzortzis Stavros , Apostolakis Stavros , Xenakis Konstantinos , Spiropoulos Georgios , Lazaridis Kyriakos
Published: November 2008

Background

Intravascular catheters provide necessary vascular access, for intravenous therapy, blood sampling and pressure monitoring. However, their use is often associated with serious local and systemic complications including local site infection, intravascular catheter-related bloodstream infections, septic thrombophlebitis, and endocarditis.

Case presentation

We present a case of a 72 year old postoperative patient presented with persistent fever. Transthoracic and transesophageal echocardiograms demonstrated a lesion in the superior vena cava, protruding into the right atrium and infiltrating the atrial septum. Candida albicans grew in blood cultures as well as in the subclavian catheter tip culture. Anti-fungal and antithrombotic therapy was initiated. After 2 weeks treatment the lesion was diminished.

Conclusion

Transthoracic and transesophageal echocardiography has been proved efficient and cost-effective in guiding therapy in cases of catheter related infections. In the presented case the lesions in vena cava and the involvement of the endocardium were early identified by echocardiography. Moreover, a follow-up echocardiogram confirmed the efficiency of the therapeutic approach.
Diarrhea, negative t-waves, fever and skin rash, rare manifestation of carbamazepine hypersensitivity: a case report
Authors: Aigner Felix , Aigner Wolfgang , Hoppichler Friedrich , Luef Gerhard , Bonatti Hugo
Published: November 2008

Introduction

Antiepileptic drug induced hypersensitivity syndrome is a rare side effect of some of the first line anticonvulsive drugs such as carbamazepine and other aromatic agents. We are the first to mention a rare case of gastrointestinal, skin and cardiac findings related to carbamazepine administration, which is very uncommon and needs to be reported.

Case presentation

We report on a 62-year-old Caucasian woman with carbamazepine associated hypersensitivity syndrome, who developed diarrhea, fever, skin lesions, pericardial effusion and pathology on electrocardiogram with terminal negative T waves in I, II, aVL, V5 and V6,. After withdrawal of carbamazepine and administration of methylprednisolone, all initial symptoms improved, white blood cell count normalized, pericardial effusion resolved and pathologic electrocardiogram findings resolved.

Conclusion

Anticonvulsive drug hypersensitivity syndromes can present with a wide spectrum of unspecific symptoms, which the prescribing clinician should be aware of.
Pedunculated uterine leiomyoma mimicking abdominal mass: a case report
Authors: Spanoudaki Athina , Oikonomou Anastasia , Dimitrova Krasimira , Prassopoulos Panos
Published: November 2008

A 48-year-old woman presented with abdominal fullness and a palpable "mass" in the left lower quadrant. Ultrasonography showed a large, rounded, hypoechoic mass. Contrast-enhanced helical CT of the abdomen demonstrated a well-circumscribed, heterogeneously but vividly enhancing mass. The uterus had a leiomyomatous configuration on CT. Uterus and mass revealed the same enhancing pattern. Thin section CT revealed a long, thin stalk connecting the mass with the body of the uterus. Surgical removal of both uterus and the mass confirmed the diagnosis of a pedunculated subserosal leiomyoma originating from a leiomyomatous uterus.
Anaesthesiologic protocol for kidney transplantation in two patients with Fabry Disease: a case series
Authors: Sorbello Massimiliano , Veroux Massimiliano , Cutuli Melania , Morello Gianluigi , Paratore Annalaura , Sidoti Mirko Tindaro , Maugeri Jessica Giuseppina , Gagliano Massimiliano , Giuffrida Giuseppe , Corona Daniela , Veroux Pierfrancesco
Published: November 2008

Fabry's Disease is a rare genetic syndrome, with a classic X-linked alpha -galactosidase A deficiency phenotype, responsible for glico-sphyngolypids metabolism impairment with clinical effects in several organs and functions. We describe the anaesthesiologic implications of two patients with Fabry disease who underwent a kidney transplantation from a deceased donor. We recommend careful preoperative evaluation, including cardiac sonography study and spirometry for Fabry disease patients, and according to our experience, we recommend advanced haemodynamic monitoring during surgery. Careful airway examination should be further performed, with particular attention to patient ventilability prediction and available alternative strategies for airway management in case of difficulties. A nephroprotective strategy and a particular care to the associated end-stage organ disease may significantly improve the long-term outcome of patients with Fabry Disease.
Heat shock protein-90-alpha, a prolactin-STAT5 target gene identified in breast cancer cells, is involved in apoptosis regulation
Authors: Perotti Christian , Liu Ruixuan , Parusel Christine T , Böcher Nadine , Schultz Jörg , Bork Peer , Pfitzner Edith , Groner Bernd , Shemanko Carrie S
Published: November 2008

Introduction

The prolactin-Janus-kinase-2-signal transducer and activator of transcription-5 (JAK2-STAT5) pathway is essential for the development and functional differentiation of the mammary gland. The pathway also has important roles in mammary tumourigenesis. Prolactin regulated target genes are not yet well defined in tumour cells, and we undertook, to the best of our knowledge, the first large genetic screen of breast cancer cells treated with or without exogenous prolactin. We hypothesise that the identification of these genes should yield insights into the mechanisms by which prolactin participates in cancer formation or progression, and possibly how it regulates normal mammary gland development.

Methods

We used subtractive hybridisation to identify a number of prolactin-regulated genes in the human mammary carcinoma cell line SKBR3. Northern blotting analysis and luciferase assays identified the gene encoding heat shock protein 90-alpha (HSP90A) as a prolactin-JAK2-STAT5 target gene, whose function was characterised using apoptosis assays.

Results

We identified a number of new prolactin-regulated genes in breast cancer cells. Focusing on HSP90A, we determined that prolactin increased HSP90A mRNA in cancerous human breast SKBR3 cells and that STAT5B preferentially activated the HSP90A promoter in reporter gene assays. Both prolactin and its downstream protein effector, HSP90α, promote survival, as shown by apoptosis assays and by the addition of the HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), in both untransformed HC11 mammary epithelial cells and SKBR3 breast cancer cells. The constitutive expression of HSP90A, however, sensitised differentiated HC11 cells to starvation-induced wild-type p53-independent apoptosis. Interestingly, in SKBR3 breast cancer cells, HSP90α promoted survival in the presence of serum but appeared to have little effect during starvation.

Conclusions

In addition to identifying new prolactin-regulated genes in breast cancer cells, we found that prolactin-JAK2-STAT5 induces expression of the HSP90A gene, which encodes the master chaperone of cancer. This identifies one mechanism by which prolactin contributes to breast cancer. Increased expression of HSP90A in breast cancer is correlated with increased cell survival and poor prognosis and HSP90α inhibitors are being tested in clinical trials as a breast cancer treatment. Our results also indicate that HSP90α promotes survival depending on the cellular conditions and state of cellular transformation.
Duration of salmeterol-induced bronchodilation in mechanically ventilated chronic obstructive pulmonary disease patients: a prospective clinical study
Authors: Malliotakis Polychronis , Linardakis Manolis , Gavriilidis George , Georgopoulos Dimitris
Published: November 2008

Introduction

Delivery of bronchodilators with a metered-dose inhaler (MDI) and a spacer device in mechanically ventilated patients has become a widespread practice. However, except for the short-acting β2-agonist salbutamol, the duration of action of other bronchodilators, including long-acting β2-agonists, delivered with this technique is not well established. The purpose of this study was to examine the duration of bronchodilation induced by the long-acting β2-agonist salmeterol administered with an MDI and a spacer in a group of mechanically ventilated patients with exacerbation of chronic obstructive pulmonary disease (COPD).

Methods

Ten mechanically ventilated patients with acute exacerbation of COPD received four puffs of salmeterol (25 μg/puff). Salmeterol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud enhance spacer. Static and dynamic airway pressures, minimum (Rint) and maximum (Rrs) inspiratory resistance, and the difference between Rrs and Rint (ΔR) were measured before and at 15, 30, and 60 minutes as well as at 2, 3, 4, 6, 8, 10, and 12 hours after salmeterol administration. The overall effects of salmeterol on respiratory system mechanics and heart rate during the 12-hour study period were analyzed by nonparametric Wilcoxon signed rank test.

Results

Salmeterol caused a significant decrease in dynamic and static airway pressures, Rint, and Rrs. These changes were evident at 30 minutes and remained significant for 8 hours after salmeterol administration. The duration of bronchodilation varied significantly among patients, lasting in some patients more than 10 hours and wearing off in others in less than 6 hours.

Conclusions

It is concluded that four puffs of salmeterol delivered with an MDI and a spacer device induces significant bronchodilation in mechanically ventilated patients with COPD exacerbation, the duration of which is highly variable, precluding definite conclusions in regard to optimum dosing schedules.