bluuebunny/crossref_metadata_2025 huggingface dataset:
Chromosomal imbalances in nasopharyngeal carcinoma: a meta-analysis of comparative genomic hybridization results
Authors: Li Xin , Wang Ena , Zhao Ying-dong , Ren Jia-Qiang , Jin Ping , Yao Kai-Tai , Marincola Francesco M
Published: January 2006

Nasopharyngeal carcinoma (NPC) is a highly prevalent disease in Southeast Asia and its prevalence is clearly affected by genetic background. Various theories have been suggested for its high incidence in this geographical region but to these days no conclusive explanation has been identified. Chromosomal imbalances identifiable through comparative genomic hybridization may shed some light on common genetic alterations that may be of relevance to the onset and progression of NPC. Review of the literature, however, reveals contradictory results among reported findings possibly related to factors associated with patient selection, stage of disease, differences in methodological details etc. To increase the power of the analysis and attempt to identify commonalities among the reported findings, we performed a meta-analysis of results described in NPC tissues based on chromosomal comparative genomic hybridization (CGH). This meta-analysis revealed consistent patters in chromosomal abnormalities that appeared to cluster in specific "hot spots" along the genome following a stage-dependent progression.
How useful are post consultation letters to patients?
Authors: Roberts Nicola J , Partridge Martyn R
Published: January 2006

Background

As part of the NHS plan it was suggested that all patients receive copies of letters sent to their General Practitioner following outpatient consultations. The former Secretary of State for Health extended this proposal, suggesting that patients have a specific letter to themselves after a hospital consultation.

Methods

The aim of this study was to send cardiorespiratory patients attending Charing Cross Hospital, a copy of the letter sent to their G.P. plus a specific letter to themselves and to assess the usefulness and comprehensibility of each. The letters were analysed for dictation time, Flesch Reading Ease Score, Flesch-Kincaid Grade Level and word count. Eighty-four out of 105 sequential patients (80%) consented and were sent both types of letter after their attendance. Patients returned both letters circling any items they did not understand and stated a preference for the GP letter, patient letter, or both. The patients' GPs were subsequently also asked for their views on each letter.

Results

GP letters took significantly longer to dictate than patient letters. The Flesch Reading Ease Score was significantly higher in the patient letters, indicating that the patient letters were easier to read. The GP letters were significantly longer than the patient letters and patients were significantly more likely to circle more items in the GP letters (p < 0.001). The content of letters is sometimes inaccurate. Thirty-six out of 62 patients (58%) would like to receive both letters, 13/62 (21.6%) would prefer the GP letter and 13/62 (20%) wanted only the patient letter. 45 GPs replied (62.5%), 28/45 (62.5%) wanted the GP letter, 14 GPs (31.1%) wanted both letters and 3/45 (6.7%) wanted the patient letter only. General themes concerned insufficient clinical details and the GPs preferred the structure of the letters written to them.

Conclusion

Patients appreciate copies of the letter being sent to their GP but comprehension is less good than with a shorter letter written especially to the patient. More attention needs to be paid to making letters to GPs simpler to read without losing the structure and detail liked by GPs. A compromise might be to dictate the letter in front of the patient and to provide a speciality-specific glossary to accompany each letter.
Serum antibodies from Parkinson's disease patients react with neuronal membrane proteins from a mouse dopaminergic cell line and affect its dopamine expression
Authors: Huber Victor C , Mondal Tapan , Factor Stewart A , Seegal Richard F , Lawrence David A
Published: January 2006

Evidence exists suggesting that the immune system may contribute to the severity of idiopathic Parkinson's disease (IPD). The data presented here demonstrates that antibodies in the sera of patients with IPD have increased binding affinity to dopaminergic (DA) neuronal (MN9D cell line) membrane antigens in comparison to antibodies in sera from healthy controls. In general, the degree of antibody reactivity to these antigens of the mouse MN9D cell line appears to correlate well with the disease severity of the IPD patients contributing sera, based on the total UPDRS scores. Surprisingly, the sera from IPD patients enhanced the DA content of MN9D cells differentiated with n-butyrate; the n-butyrate-differentiated MN9D cells had a greater concentration of DA (DA/mg total protein) than undifferentiated MN9D cells, especially early in culture. Although the IPD sera did not directly harm MN9D cellular viability or DA production, in the presence of the N9 microglial cell line, the amount of DA present in cultures of untreated or n-butyrate-treated MN9D cells was lowered by the IPD sera. The results suggest the involvement of antibodies in the decline of dopamine production and, thus, the potential of immune system participation in IPD.
Memory in astrocytes: a hypothesis
Authors: Caudle Robert M
Published: January 2006

Background

Recent work has indicated an increasingly complex role for astrocytes in the central nervous system. Astrocytes are now known to exchange information with neurons at synaptic junctions and to alter the information processing capabilities of the neurons. As an extension of this trend a hypothesis was proposed that astrocytes function to store information. To explore this idea the ion channels in biological membranes were compared to models known as cellular automata. These comparisons were made to test the hypothesis that ion channels in the membranes of astrocytes form a dynamic information storage device.

Results

Two dimensional cellular automata were found to behave similarly to ion channels in a membrane when they function at the boundary between order and chaos. The length of time information is stored in this class of cellular automata is exponentially related to the number of units. Therefore the length of time biological ion channels store information was plotted versus the estimated number of ion channels in the tissue. This analysis indicates that there is an exponential relationship between memory and the number of ion channels. Extrapolation of this relationship to the estimated number of ion channels in the astrocytes of a human brain indicates that memory can be stored in this system for an entire life span. Interestingly, this information is not affixed to any physical structure, but is stored as an organization of the activity of the ion channels. Further analysis of two dimensional cellular automata also demonstrates that these systems have both associative and temporal memory capabilities.

Conclusion

It is concluded that astrocytes may serve as a dynamic information sink for neurons. The memory in the astrocytes is stored by organizing the activity of ion channels and is not associated with a physical location such as a synapse. In order for this form of memory to be of significant duration it is necessary that the ion channels in the astrocyte syncytium be electrically in contact with each other. This function may be served by astrocyte gap junctions and suggests that agents that selectively block these gap junctions should disrupt memory.
Latency: the hidden HIV-1 challenge
Authors: Marcello Alessandro
Published: January 2006

Eradication of HIV-1 from an infected individual cannot be achieved by current regimens. Viral reservoirs established early during the infection remain unaffected by anti-retroviral therapy for a long time and are able to replenish systemic infection upon interruption of the treatment. Therapeutic targeting of viral latency will require a better understanding of the basic mechanisms underlying the establishment and long-term maintenance of HIV-1 in resting memory CD4 T cells, the most prominent reservoir of transcriptionally silent provirus. Since the molecular mechanisms that permit long term transcriptional control of proviral gene expression in these cells are still obscure, this review aims at summarizing the various aspects of the problem that need to be considered. In particular, this review will focus the attention on the control of transcription imposed by chromatin through various epigenetic mechanisms. Exploring the molecular details of viral latency will provide new insights for eventual future therapeutics that aim at viral eradication.
Review of "The Twelfth West Coast Retrovirus Meeting" and "The Twenty-third Annual Symposium on Nonhuman Primate Models for AIDS"
Authors: Scott Cairns J
Published: January 2006

Two recent meetings held on the west coast of the USA highlighted current work being done in the field of retrovirology and AIDS. The meetings, "The Twelfth West Coast Retrovirus Meeting" (Palm Springs CA; October 6–8, 2005), and the "Twenty-third Annual Symposium on Nonhuman Primate Models for AIDS" (Portland OR; September 21–24) covered a broad range of topics. The highlights covered here are not meant to be inclusive but reflect presentations of interest in the identification and development of new HIV therapies and the role played by animal models in their development.
Two Surgeon General's reports on smoking and cancer: a historical investigation of the practice of causal inference
Authors: Parascandola Mark , Weed Douglas L , Dasgupta Abhijit
Published: January 2006

Background

The epidemiologic literature is replete with conceptual discussions about causal inference, but little is known about how the causal criteria are applied in public health practice. The criteria for causal inference in use today by epidemiologists have been shaped substantially by their use over time in reports of the U.S. Surgeon General on Smoking and Health.

Methods

We reviewed two classic reports on smoking and health from expert committees convened by the US Surgeon General, in 1964 and 1982, in order to evaluate and contrast how the committees applied causal criteria to the available evidence for the different cancer sites at different time periods. We focus on the evidence for four cancer sites in particular that received detailed reviews in the reports: lung, larynx, esophagus and bladder.

Results

We found that strength of association and coherence (especially dose-response, biological plausibility and epidemiologic sense) appeared to carry the most weight; consistency carried less weight, and temporality and specificity were apparently not applied at all in some cases. No causal claim was made for associations with a summary odds ratio of less than 3.0.

Conclusion

Our findings suggest that the causal criteria as described in textbooks and the Surgeon General reports can have variable interpretations and applications in practice. While the authors of these reports may have considered evidential factors that they did not explicitly cite, such lack of transparency of methods undermines the purpose of the causal criteria to promote objective, evidence-based decision making. Further empirical study and critical examination of the process by which causal conclusions are reached can play an important role in advancing the practice of epidemiology by helping public health scientists to better understand the practice of causal inference.
Comparison of isocaloric very low carbohydrate/high saturated fat and high carbohydrate/low saturated fat diets on body composition and cardiovascular risk
Authors: Noakes Manny , Foster Paul R , Keogh Jennifer B , James Anthony P , Mamo John C , Clifton Peter M
Published: January 2006

Background

It is speculated that high saturated fat very low carbohydrate diets (VLCARB) have adverse effects on cardiovascular risk but evidence for this in controlled studies is lacking. The objective of this study was to compare, under isocaloric conditions, the effects of a VLCARB to 2 low saturated fat high carbohydrate diets on body composition and cardiovascular risk.

Methods

Eighty three subjects, 48 ± 8 y, total cholesterol 5.9 ± 1.0 mmol/L, BMI 33 ± 3 kg/m2 were randomly allocated to one of 3 isocaloric weight loss diets (6 MJ) for 8 weeks and on the same diets in energy balance for 4 weeks: Very Low Fat (VLF) (CHO:Fat:Protein; %SF = 70:10:20; 3%), High Unsaturated Fat (HUF) = (50:30:20; 6%), VLCARB (4:61:35; 20%)

Results

Percent fat mass loss was not different between diets VLCARB -4.5 ± 0.5, VLF-4.0 ± 0.5, HUF -4.4 ± 0.6 kg). Lean mass loss was 32-31% on VLCARB and VLF compared to HUF (21%) (P < 0.05). LDL-C increased significantly only on VLCARB by 7% (p < 0.001 compared with the other diets) but apoB was unchanged on this diet and HDL-C increased relative to the other 2 diets. Triacylglycerol was lowered by 0.73 ± 0.12 mmol/L on VLCARB compared to -0.15 ± 0.07 mmol/L on HUF and -0.06 ± 0.13 mmol/L on VLF (P < 0.001). Plasma homocysteine increased 6.6% only on VLCARB (P = 0.026). VLCARB lowered fasting insulin 33% compared to a 19% fall on HUF and no change on VLF (P < 0.001). The VLCARB meal also provoked significantly lower post prandial glucose and insulin responses than the VLF and HUF meals. All diets decreased fasting glucose, blood pressure and CRP (P < 0.05).

Conclusion

Isocaloric VLCARB results in similar fat loss than diets low in saturated fat, but are more effective in improving triacylglycerols, HDL-C, fasting and post prandial glucose and insulin concentrations. VLCARB may be useful in the short-term management of subjects with insulin resistance and hypertriacylglycerolemia.
Absorption and metabolism of conjugated α-linolenic acid given as free fatty acids or triacylglycerols in rats
Authors: Plourde Mélanie , Sergiel Jean-Pierre , Chardigny Jean-Michel , Grégoire Stéphane , Angers Paul , Sébédio Jean-Louis
Published: January 2006

Background

Conjugated linoleic acid (CLA) is a group of polyunsaturated fatty acids which have been extensively studied in the past two decades. However, conjugated octadecatrienoic acid such as cis-9,trans-11,cis-15 and cis-9,trans-13,cis-15, recently identified, have not been extensively investigated. This work presents bioavailability and tissue incorporation of a mixture of conjugated octadecatrienoic (CLnA) acids ingested as free fatty acids (FFA) and triacylglycerols (TAG).

Results

Male Wistar rats were fed rumenic acid (RA: cis-9,trans-11 18:2) and a CLnA mixture (cis-9,trans-11,cis-15 18:3 and cis-9,trans-13,cis-15 18:3) as FFA and TAG for 8 days. RA and CLnA were both totally absorbed when given as FFA as well as TAG. Both isomers of CLnA as FFA or TAG were incorporated into neutral lipids. Metabolites up to 22:6 conjugated isomers were present in liver and plasma phospholipids of rats fed the CLnA diets.

Conclusion

Finally, CLnA are as well absorbed as RA in vivo and their incorporation into tissues and bioconversion are similar when ingested as FFA or as TAG.
Selective Up-Regulation of NMDA-NR1 Receptor Expression in Myenteric Plexus after TNBS Induced Colitis in Rats
Authors: Zhou QiQi , Caudle Robert M , Price Donald D , Del Valle-Pinero Arseima Y , Verne G Nicholas
Published: January 2006

Background

N-methyl-D-aspartic acid (NMDA) spinal cord receptors play an important role in the development of hyperalgesia following inflammation. It is unclear, however, if changes in NMDA subunit receptor gene expression in the colonic myenteric plexus are associated with colonic inflammation. We investigated regulation of NMDA-NR1 receptor gene expression in TNBS induced colitis in rats. Male Sprague-Dawley rats (150 g–250 g) were treated with 20 mg trinitrobenzene sulfonic acid (TNBS) diluted in 50% ethanol. The agents were delivered with a 24 gauge catheter inserted into the lumen of the colon. The animals were sacrificed at 2, 7, 14, 21, and 28 days after induction of the colitis, their descending colon was retrieved for reverse transcription-polymerase chain reaction; a subset of animals' distal colon was used for two-dimensional (2-D) western analysis and immunocytochemistry.

Results

NR1-exon 5 (N1) and NR1-exon 21 (C1) appeared 14, 21 and 28 days after TNBS treatment. NR1 pan mRNA was up-regulated at 14, 21, and 28 days. The NR1-exon 22 (C2) mRNA did not show significant changes. Using 2-D western analysis, untreated control rats were found to express only NR1001 whereas TNBS treated rats expressed NR1001, NR1011, and NR1111. Immunocytochemistry demonstrated NR1-N1 and NR1-C1 to be present in the myenteric plexus of TNBS treated rats.

Conclusion

These results suggest a role for colonic myenteric plexus NMDA receptors in the development of neuronal plasticity and visceral hypersensitivity in the colon. Up-regulation of NMDA receptor subunits may reflect part of the basis for chronic visceral hypersensitivity in conditions such as post-infectious irritable bowel syndrome.
Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats
Authors: Yang Pamela B , Swann Alan C , Dafny Nachum
Published: January 2006

Background

Methylphenidate (MPD) is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA), nucleus accumbens (NAc), and prefrontal cortex (PFC).

Methods

The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg) on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39) rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p.) on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10). Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min.

Results

Results showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% ± 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% ± 5.9% after 2.5 mg/kg MPD, and 56.5% ± 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of MPD-induced attenuation were also found among these brain areas.

Conclusion

These results suggest that an acute treatment of MPD produces electrophysiologically detectable alterations at the neuronal level, as well as observable, behavioral responses. The present study is the first to investigate the acute dose-response effects of MPD on behavior in terms of locomotor activity and in the brain involving the sensory inputs of VTA, NAc, and PFC neurons in intact, non-anesthetized, freely behaving rats previously implanted with permanent electrodes.
Prophylactic antibiotic for prevention of posttraumatic meningitis after traumatic pneumocephalus: design and rationale of a placebo-controlled randomized multicenter trial [ISRCTN71132784]
Authors: Eftekhar Behzad , Ghodsi Mohammad , Hadadi Azar , Taghipoor Mousa , Sigarchi Samira Zabihyan , Rahimi-Movaghar Vafa , Kazemzadeh Ehsan Sherafat , Esmaeeli Babak , Nejat Farideh , Yalda Alireza , Ketabchi Ebrahim
Published: January 2006

Background

The purpose of this study is to compare the efficacy of prophylactic antibiotic for prevention of meningitis in acute traumatic pneumocephalus patients.

Methods

In this prospective, randomized controlled clinical trial, 200 selected head injury patients with traumatic pneumocephalus are randomly assigned to receive intravenous antibiotics (2 grams Ceftriaxone twice a day), oral antibiotics (Azithromycin) or placebo for at least 7 days after trauma. The patients will be followed for one month posttrauma.

Conclusion

The authors hope that this study helps clarifying the effectiveness and indications of antibiotics in prevention of meningitis in traumatic pneumocephalus after head injury and in specific subgroup of these patients.
Improvement in hearing after chiropractic care: a case series
Authors: Di Duro Joseph O
Published: January 2006

Background

The first chiropractic adjustment given in 1895 was reported to have cured deafness. This study examined the effects of a single, initial chiropractic visit on the central nervous system by documenting clinical changes of audiometry in patients after chiropractic care.

Case presentation

Fifteen patients are presented (9 male, 6 female) with a mean age of 54.3 (range 34–71). A Welch Allyn AudioScope 3 was used to screen frequencies of 1000, 2000, 4000 and 500 Hz respectively at three standard decibel levels 20 decibels (dB), 25 dB and 40 dB, respectively, before and immediately after the first chiropractic intervention. Several criteria were used to determine hearing impairment. Ventry & Weinstein criteria of missing one or more tones in either ear at 40 dB and Speech-frequency criteria of missing one or more tones in either ear at 25 dB.

All patients were classified as hearing impaired though greater on the right. At 40 dB using the Ventry & Weinstein criteria, 6 had hearing restored, 7 improved and 2 had no change. At 25 dB using the Speech-frequency criteria, none were restored, 11 improved, 4 had no change and 3 missed a tone.

Conclusion

A percentage of patients presenting to the chiropractor have a mild to moderate hearing loss, most notably in the right ear. The clinical progress documented in this report suggests that manipulation delivered to the neuromusculoskeletal system may create central plastic changes in the auditory system.
Saline Systems highlights for 2005
Authors: DasSarma Shiladitya
Published: January 2006

On the 4th of July, 2005, the Saline Systems editorial group launched the new online open access journal, Saline Systems, with BioMed Central as the publisher. The scope of the journal includes both basic and applied research on halophilic organisms and saline environments, from gene systems to ecosystems. The stated goal of the journal is to meet publication needs for researchers working in coastal and inland saline environments and provide an interdisciplinary and readily accessible forum for scientists worldwide. The inaugural volume of the journal contains a significant number of high quality original research papers and reviews on a wide range of relevant topics. At the end of the launch period, from January 1, 2006 onwards, the journal will be introducing article-processing charges to cover the cost of publication. Charges will be partly or completely waived for authors from BioMed Central institutional subscribers and in cases of financial hardship.
MIAME/Plant – adding value to plant microarrray experiments
Authors: Zimmermann Philip , Schildknecht Beatrice , Craigon David , Garcia-Hernandez Margarita , Gruissem Wilhelm , May Sean , Mukherjee Gaurab , Parkinson Helen , Rhee Seung , Wagner Ulrich , Hennig Lars
Published: January 2006

Appropriate biological interpretation of microarray data calls for relevant experimental annotation. The widely accepted MIAME guidelines provide a generic, organism-independant standard for minimal information about microarray experiments. In its overall structure, MIAME is very general and specifications cover mostly technical aspects, while relevant organism-specific information useful to understand the underlying experiments is largely missing. If plant biologists want to use results from published microarray experiments, they need detailed information about biological aspects, such as growth conditions, harvesting time or harvested organ(s). Here, we propose MIAME/Plant, a standard describing which biological details to be captured for describing microarray experiments involving plants. We expect that a more detailed and more systematic annotation of microarray experiments will greatly increase the use of transcriptome data sets for the scientific community. The power and value of systematic annotation of microarray data is convincingly demonstrated by data warehouses such as Genevestigator® or NASCArrays, and better experimental annotation will make these applications even more powerful.
Science and policy in substance abuse
Authors: Arndt Stephan
Published: January 2006

Substance Abuse Treatment, Prevention, and Policy (SATPP) is an open access, peer-reviewed international journal of original research and scholarship that focuses on policy issues in the treatment and prevention of substance use disorders. Separate and often disparate public systems deal with substance use problems as well as provide treatment and prevention. This journal will provide an environment for the exchange of ideas, new research, consensus papers, and critical reviews that bridge fields that share a common goal of reducing the problems caused by drugs and alcohol. The agenda is simple; a new forum for integrating thoughts, issues, and developments.
Cannabis, motivation, and life satisfaction in an internet sample
Authors: Barnwell Sara Smucker , Earleywine Mitch , Wilcox Rand
Published: January 2006

Although little evidence supports cannabis-induced amotivational syndrome, sources continue to assert that the drug saps motivation [1], which may guide current prohibitions. Few studies report low motivation in chronic users; another reveals that they have higher subjective wellbeing. To assess differences in motivation and subjective wellbeing, we used a large sample (N = 487) and strict definitions of cannabis use (7 days/week) and abstinence (never). Standard statistical techniques showed no differences. Robust statistical methods controlling for heteroscedasticity, non-normality and extreme values found no differences in motivation but a small difference in subjective wellbeing. Medical users of cannabis reporting health problems tended to account for a significant portion of subjective wellbeing differences, suggesting that illness decreased wellbeing. All p-values were above p = .05. Thus, daily use of cannabis does not impair motivation. Its impact on subjective wellbeing is small and may actually reflect lower wellbeing due to medical symptoms rather than actual consumption of the plant.
First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib [NCT00267215]
Authors: Wittenberg Ralf H , Schell Ernest , Krehan Gerhard , Maeumbaed Roland , Runge Hans , Schlüter Peter , Fashola Taiwo OA , Thurston Helen J , Burger Klaus J , Trechsel Ulrich
Published: January 2006

Cyclo-oxygenase-2 selective inhibitors are frequently used to manage osteoarthritis. We compared the analgesic efficacy of the novel cyclo-oxygenase-2 selective inhibitor lumiracoxib (Prexige®) versus placebo and celecoxib in patients with knee osteoarthritis. This seven day, double-blind, placebo and active comparator controlled, parallel group study included 364 patients aged ≥50 years with moderate-to-severe symptomatic knee osteoarthritis. Patients received lumiracoxib 400 mg/day (four times the recommended chronic dose in osteoarthritis; n = 144), placebo (n = 75), or celecoxib 200 mg twice daily (n = 145). The primary variable was actual pain intensity difference (100 mm visual–analogue scale) between baseline and the mean of three hour and five hour assessments after the first dose. Actual pain intensity difference, average and worst pain, pain relief and functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC™]) were measured over seven days. Patients also completed a global evaluation of treatment effect at study end or premature discontinuation. For the primary variable, the superiority of lumiracoxib versus placebo, the noninferiority of lumiracoxib versus celecoxib, and the superiority of lumiracoxib versus celecoxib were assessed by closed test procedure adjusting for multiplicity, thereby maintaining the overall 5% significance level. In addition, celecoxib was assessed versus placebo in a predefined exploratory manner to assess trial sensitivity. Lumiracoxib provided better analgesia than placebo 3–5 hours after the first dose (P = 0.004) through to study end. The estimated difference between lumiracoxib and celecoxib 3–5 hours after the first dose was not significant (P = 0.185). Celecoxib was not significantly different from placebo in this analysis (P = 0.069). At study end 13.9% of lumiracoxib-treated patients reported complete pain relief versus 5.5% and 5.3% of celecoxib and placebo recipients, respectively. WOMAC™ total and subscales improved for both active treatments versus placebo except for difficulty in performing daily activities, for which celecoxib just failed to achieve significance (P = 0.056). In the patient's global evaluation of treatment effect, 58.1% of patients receiving lumiracoxib rated treatment as 'excellent' or 'good', versus 48.6% of celecoxib and 25.3% of placebo patients. Lumiracoxib was well tolerated. The overall incidence of adverse events was similar across treatment groups.
Switching TNF antagonists in patients with chronic arthritis: an observational study of 488 patients over a four-year period
Authors: Gomez-Reino Juan J , Carmona Loreto ,   the BIOBADASER Group
Published: January 2006

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34–0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97–2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13–4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications.
Identification of blood biomarkers of rheumatoid arthritis by transcript profiling of peripheral blood mononuclear cells from the rat collagen-induced arthritis model
Authors: Shou Jianyong , Bull Christopher M , Li Li , Qian Hui-Rong , Wei Tao , Luo Shuang , Perkins Douglas , Solenberg Patricia J , Tan Seng-Lai , Chen Xin-Yi Cynthia , Roehm Neal W , Wolos Jeffrey A , Onyia Jude E
Published: January 2006

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease that results in joint destruction and subsequent loss of function. To better understand its pathogenesis and to facilitate the search for novel RA therapeutics, we profiled the rat model of collagen-induced arthritis (CIA) to discover and characterize blood biomarkers for RA. Peripheral blood mononuclear cells (PBMCs) were purified using a Ficoll gradient at various time points after type II collagen immunization for RNA preparation. Total RNA was processed for a microarray analysis using Affymetrix GeneChip technology. Statistical comparison analyses identified differentially expressed genes that distinguished CIA from control rats. Clustering analyses indicated that gene expression patterns correlated with laboratory indices of disease progression. A set of 28 probe sets showed significant differences in expression between blood from arthritic rats and that from controls at the earliest time after induction, and the difference persisted for the entire time course. Gene Ontology comparison of the present study with previous published murine microarray studies showed conserved Biological Processes during disease induction between the local joint and PBMC responses. Genes known to be involved in autoimmune response and arthritis, such as those encoding Galectin-3, Versican, and Socs3, were identified and validated by quantitative TaqMan RT-PCR analysis using independent blood samples. Finally, immunoblot analysis confirmed that Galectin-3 was secreted over time in plasma as well as in supernatant of cultured tissue synoviocytes of the arthritic rats, which is consistent with disease progression. Our data indicate that gene expression in PBMCs from the CIA model can be utilized to identify candidate blood biomarkers for RA.
No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjögren's syndrome
Authors: Gottenberg Jacques-Eric , Sellam Jérémie , Ittah Marc , Lavie Frédéric , Proust Alexis , Zouali Habib , Sordet Christelle , Sibilia Jean , Kimberly Robert P , Mariette Xavier , Miceli-Richard Corinne
Published: January 2006

Polyclonal B cell activation might be related to pathogenic over-expression of B-cell-activating factor (BAFF) in primary Sjögren's syndrome (pSS) and other autoimmune diseases. We therefore investigated whether BAFF over-expression in pSS could be a primary, genetically determined event that leads to the disease. The complete BAFF gene was sequenced in Caucasian pSS patients and control individuals. The only single nucleotide polymorphism frequently observed, namely -871 T/C in the promoter region, was then genotyped in 162 French patients with pSS and 90 French control individuals. No significant differences in allele (T allele frequency: 49.7% in patients with pSS versus 50% in controls; P = 0.94) and genotype frequencies of BAFF polymorphism were detected between pSS patients and control individuals. BAFF gene polymorphism was not associated with a specific pattern of antibody secretion either. T allele carriers had significantly increased BAFF protein serum levels (mean values of 8.6 and 5.7 ng/ml in patients with TT and TC genotypes, respectively, versus 3.3 ng/ml in patients with CC genotype; P = 0.01), although no correlation was observed between BAFF polymorphism and mRNA level. In conclusion, BAFF gene polymorphism is neither involved in genetic predisposition to pSS nor associated with a specific pattern of antibody production.
The induction of CCN2 by TGFβ1 involves Ets-1
Authors: Van Beek Jonathan P , Kennedy Laura , Rockel Jason S , Bernier Suzanne M , Leask Andrew
Published: January 2006

CCN2 is encoded by an immediate-early gene induced in mesenchymal cells during the formation of blood vessels, bone and connective tissue. It plays key roles in cell adhesion and migration, as well as matrix remodeling. CCN2 is overexpressed in fibrosis, arthritis and cancer; thus, an understanding of how to control CCN2 expression is likely to have importance in developing therapies to combat these pathologies. Previously, we found that the promoter sequence GAGGAATG is important for Ccn2 gene regulation in NIH 3T3 fibroblasts. In this report, we show that this sequence mediates activation of the CCN2 promoter by the ETS family of transcription factors. Endogenous Ets-1 binds this element of the CCN2 promoter, and dominant negative Ets-1 and specific Ets-1 small interfering RNA block induction of CCN2 expression by TGFβ. In the absence of added TGFβ1, Ets-1, but not the related fli-1, synergizes with Smad 3 to activate the CCN2 promoter. Whereas the ability of transfected Ets-1 to activate the CCN2 promoter is dependent on protein kinase C (PKC), Ets-1 in the presence of co-transfected Smad3 does not require PKC, suggesting that the presence of Smad3 bypasses the requirement of Ets-1 for PKC to activate target promoter activity. Our results are consistent with the notion that Smad3 and Ets-1 cooperate in the induction of the CCN2 promoter by TGFβ1. Antagonizing Ets-1 might be of benefit in attenuating CCN2 expression in fibrosis, arthritis and cancer, and may be useful in modulating the outcome of these disorders.
CD95-induced osteoarthritic chondrocyte apoptosis and necrosis: dependency on p38 mitogen-activated protein kinase
Authors: Wei Lei , Sun Xiao-juan , Wang Zhengke , Chen Qian
Published: January 2006

One of the hallmarks of osteoarthritic cartilage is the loss of chondrocyte cellularity due to cell death. However, considerable controversy has recently arisen surrounding the extent of apoptotic cell death involved in development of osteoarthritis (OA). To shed light on this issue, we characterized cell death in primary OA chondrocytes mediated by the CD95 (Fas) pathway. Treatment of chondrocytes with anti-CD95 not only increased the rate of cell death but also increased the production of CD95 ligand by chondrocytes. This reveals a novel autocrine regulatory loop whereby activated chondrocytes may amplify CD95 signals by inducing synthesis of CD95 ligand. Multiple morphologic detection analyses indicated that apoptosis accounted for only a portion of chondrocyte death, whereas the other chondrocytes died by necrosis. Both chondrocyte apoptosis and necrosis depended on the activity of p38 mitogen-activated protein kinase (MAPK) within chondrocytes. Treatment of chondrocytes with the p38 MAPK inhibitor SB203580 abolished anti-CD95 induced cell death by inhibiting the activities of activating transcription factor-2 and caspase-3. In addition, inhibition of p38 MAPK activity in chondrocytes stimulated chondrocyte proliferation, as indicated by 5-bromo-2-deoxyuridine (BrdU) index. Thus, p38 MAPK is a potential therapeutic target, inhibition of which may maintain the cellularity of articular chondrocytes by inhibiting cell death and its amplification signal and by increasing cell proliferation.
Inhaled beta-2 agonist salbutamol and acute lung injury: an association with improvement in acute lung injury
Authors: Manocha Sanjay , Gordon Anthony C , Salehifar Ebrahim , Groshaus Horacio , Walley Keith R , Russell James A
Published: January 2006

Introduction

β2 agonists have several properties that could be beneficial in acute lung injury (ALI). We therefore chose to study the effect of inhaled β2 agonist use (salbutamol) on duration and severity of ALI.

Methods

We undertook a retrospective chart review of 86 consecutive mechanically ventilated patients with ALI, who had varying exposure to inhaled salbutamol. The cohort was divided into two groups according to the average daily dose of inhaled salbutamol they received ('high dose' ≥ 2.2 mg/day and 'low dose' <2.2 mg/day). Severity of ALI and non-pulmonary organ dysfunction was compared between the groups by calculating the days alive and free of ALI and other organ dysfunctions.

Results

The high dose and low dose groups received a mean of 3.72 mg and 0.64 mg salbutamol per day, respectively. The high dose salbutamol group had significantly more days alive and free of ALI than the low dose group (12.2 ± 4.4 days versus 7.6 ± 1.9 days, p = 0.02). There were no associations between dose of β agonist and non-pulmonary organ dysfunctions. High dose salbutamol (p = 0.04), APACHE II score (p = 0.02), and cause of ALI (p = 0.02) were independent variables associated with number of days alive and free of ALI in a multivariate linear regression model.

Conclusion

Our retrospective study suggests that salbutamol, an inhaled β2 agonist, is associated with a shorter duration and lower severity of ALI. A dose greater than 2.2 mg/day of inhaled salbutamol could be a minimal effective dose to evaluate in a randomized controlled trial.
Levosimendan may improve survival in patients requiring mechanical assist devices for post-cardiotomy heart failure
Authors: Braun Jan-Peter , Jasulaitis Dominik , Moshirzadeh Maryam , Doepfmer Ulrich R , Kastrup Marc , von Heymann Christian , Dohmen Pascal M , Konertz Wolfgang , Spies Claudia
Published: January 2006

Introduction

Most case series suggest that less than half of the patients receiving a mechanical cardiac assist device as a bridge to recovery due to severe post-cardiotomy heart failure survive to hospital discharge. Levosimendan is the only inotropic substance known to improve medium term survival in patients suffering from severe heart failure.

Methods

This retrospective analysis covers our single centre experience. Between July 2000 and December 2004, 41 consecutive patients were treated for this complication. Of these, 38 patients are included in this retrospective analysis as 3 patients died in the operating room. Levosimendan was added to the treatment protocol for the last nine patients.

Results

Of 29 patients treated without levosimendan, 20 could be weaned off the device, 9 survived to intensive care unit discharge, 7 left hospital alive and 3 survived 180 days. All 9 patients treated with levosimendan could be weaned, 8 were discharged alive from ICU and hospital, and 7 lived 180 days after surgery (p < 0.002 for 180 day survival). Plasma lactate after explantation of the device was significantly lower (p = 0.002), as were epinephrine doses. Time spent on renal replacement therapy was significantly shorter (p = 0.023).

Conclusion

Levosimendan seems to improve medium term survival in patients failing to wean off cardiopulmonary bypass and requiring cardiac assist devices as a bridge to recovery. This retrospective analysis justifies prospective randomised investigations of levosimendan in this group of patients.
Challenging the spliceosome machine
Authors: Weir Michael , Eaton Matthew , Rice Michael
Published: January 2006

Background

Using cDNA copies of transcripts and corresponding genomic sequences from the Berkeley Drosophila Genome Project, a set of 24,753 donor and acceptor splice sites were computed with a scanning algorithm that tested for single nucleotide insertion, deletion and substitution polymorphisms. Using this dataset, we developed a progressive partitioning approach to examining the effects of challenging the spliceosome system.

Results

Our analysis shows that information content increases near splice sites flanking progressively longer introns and exons, suggesting that longer splice elements require stronger binding of spliceosome components. Information also increases at splice sites near very short introns and exons, suggesting that short splice elements have crowding problems. We observe that the information found at individual splice sites depends upon a balance of splice element lengths in the vicinity, including both flanking and non-adjacent introns and exons.

Conclusion

These results suggest an interdependence of multiple splicing events along the pre-mRNA, which may have implications for how the macromolecular spliceosome machine processes sets of neighboring splice sites.
Loss of LIN-35, the Caenorhabditis elegansortholog of the tumor suppressor p105Rb, results in enhanced RNA interference
Authors: Lehner Ben , Calixto Andrea , Crombie Catriona , Tischler Julia , Fortunato Angelo , Chalfie Martin , Fraser Andrew G
Published: January 2006

Background

Genome-wide RNA interference (RNAi) screening is a very powerful tool for analyzing gene function in vivo in Caenorhabditis elegans. The effectiveness of RNAi varies from gene to gene, however, and neuronally expressed genes are largely refractive to RNAi in wild-type worms.

Results

We found that C. elegans strains carrying mutations in lin-35, the worm ortholog of the tumor suppressor gene p105Rb, or a subset of the genetically related synMuv B family of chromatin-modifying genes, show increased strength and penetrance for many germline, embryonic, and post-embryonic RNAi phenotypes, including neuronal RNAi phenotypes. Mutations in these same genes also enhance somatic transgene silencing via an RNAi-dependent mechanism. Two genes, mes-4 and zfp-1, are required both for the vulval lineage defects resulting from mutations in synMuv B genes and for RNAi, suggesting a common mechanism for the function of synMuv B genes in vulval development and in regulating RNAi. Enhanced RNAi in the germline of lin-35 worms suggests that misexpression of germline genes in somatic cells cannot alone account for the enhanced RNAi observed in this strain.

Conclusion

A worm strain with a null mutation in lin-35 is more sensitive to RNAi than any other previously described single mutant strain, and so will prove very useful for future genome-wide RNAi screens, particularly for identifying genes with neuronal functions. As lin-35 is the worm ortholog of the mammalian tumor suppressor gene p105Rb, misregulation of RNAi may be important during human oncogenesis.
Solid Synthesis of CsxH3−xPW12O40 Salts and Their Catalytic Activity for the Isomerization of n-Butane
Authors: Zou Yan , Yue Bin , Zhang Bin , He Heyong
Published: January 2006

CsxH3−xPW12O40 salts prepared by a simple solid-synthesis method show good catalytic activity in n-butane isomerization as those analogues prepared by traditional liquid-preparation method.
Development of Ordered Calcium Carbonate Microarrays from Polymorph Specific Planar Films
Authors: Kotachi Akiko , Imai Hiroaki
Published: January 2006

Ordered microarrays of rectangular calcite, platy vaterite and spicular aragonite were selectively obtained through overgrowth from planar films prepared with polymeric species. We successfully visualized the polymorphs of the calcium carbonate films using the overgrowth technique.
Two-parameter Analysis of Solvent Effects on Selectivity in Chemical Reactions: Information of Polarity and Activation Volume at the Transition State in Organic and Enzymatic Reactions
Authors: Lin Chunlei , Hiraga Yoshikazu , Ohkata Katsuo
Published: January 2006

The solvent effects on stereoselectivity in the Diels–Alder reaction of cyclopentadiene, the [2 + 2]photodimerization of 2-cyclopentenone, and the enzymatic asymmetrization of prochiral 1,3-propanediols were analyzed by two-parameter treatment using both the dielectric constant and the solubility parameter to show a good linear relationship.
Fabrication of Gold Nanosheet and Nanowire by Oxygen Plasma Induced Fusion of Densely Arrayed Nanoparticles
Authors: Onoue Shin-ya , He Junhui , Kunitake Toyoki
Published: January 2006

Densely assembled gold nanoparticles were treated by low temperature oxygen plasma to undergo complete fusion due to removal of organic protecting groups. Nanosheet and nanowire of gold with thicknesses of less than 10 nm were formed at room temperature without oxidation. Their sizes reached more than several hundred nanometers, demonstrating the effectiveness of the current method to fabricate nanoscopic architectures of mesoscopic sizes.