bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating KL-6, a biomarker of lung injury, in obstructive sleep apnoea
Authors: Lederer D. J. , Jelic S. , Basner R. C. , Ishizaka A. , Bhattacharya J. 
Published: March 2009

In obstructive sleep apnoea (OSA), oxidative stress contributes to endothelial dysfunction in the peripheral circulation. In the lung, oxidative stress can lead to alveolar injury. The present authors hypothesised that patients with OSA would have biomarker evidence of increased alveolar wall permeability.Sleep characteristics, brachial artery flow-mediated dilation and plasma KL-6 levels were observed in 11 otherwise healthy patients with OSA and 10 controls.Median (interquartile range) plasma KL-6 levels were higher in patients with OSA compared with controls: 317 (232–506) U·mL−1versus226 (179–257) U·mL−1, respectively. Higher plasma KL-6 levels were associated with greater time spent asleep with an oxyhaemoglobin saturation <90%, lower nadir saturation, more frequent desaturation of >4% during sleep and lower brachial artery flow-mediated dilation. Adjustment for nadir saturation or flow-mediated dilation attenuated the association between plasma KL-6 levels and OSA.Circulating KL-6 levels are elevated in some patients with obstructive sleep apnoea, possibly reflecting increased alveolar wall permeability.
Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement: Table 1—
Authors: Antoniou K. M. , Margaritopoulos G. , Economidou F. , Siafakas N. M. 
Published: March 2009

The connective tissue disorders (CTDs), also called collagen vascular diseases (CVDs), represent a heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs. Individuals with a CTD (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, polymyositis/dermatomyositis and mixed connective tissue disease) are susceptible to respiratory involvement. When the lungs are affected, an increasing mortality and morbidity in CVDs occurs. Interstitial lung disease (ILD) is established as a clinical corollary across the spectrum of CTDs, with an overall incidence estimated at 15%.Therefore, pivotal clinical dilemmas remain in the evaluation and management of ILD involvement in CVDs. Critical questions are the presence of fibrosis and whether the disease is clinically significant. Moreover, the clinician has to decide if treatment is warranted and which is the best therapeutic approach. The use of additional tests, such as pulmonary function tests, high-resolution computed tomography scan, bronchoalveolar lavage fluid and surgical lung biopsy, deserves better discussion. The present review focuses on establishing the diagnosis of ILD in CTD, and on evaluating disease activity and prognosis. This will provide the basis for therapeutic decisions that will be discussed, including an overview of recent advances.
Characterisation of the paralytic shellfish toxin biosynthesis gene clusters in Anabaena circinalis AWQC131C and Aphanizomenon sp. NH-5
Authors: Mihali Troco K , Kellmann Ralf , Neilan Brett A 
Published: March 2009

Abstract

Background
Saxitoxin and its analogues collectively known as the paralytic shellfish toxins (PSTs) are neurotoxic alkaloids and are the cause of the syndrome named paralytic shellfish poisoning. PSTs are produced by a unique biosynthetic pathway, which involves reactions that are rare in microbial metabolic pathways. Nevertheless, distantly related organisms such as dinoflagellates and cyanobacteria appear to produce these toxins using the same pathway. Hypothesised explanations for such an unusual phylogenetic distribution of this shared uncommon metabolic pathway, include a polyphyletic origin, an involvement of symbiotic bacteria, and horizontal gene transfer.

Results
We describe the identification, annotation and bioinformatic characterisation of the putative paralytic shellfish toxin biosynthesis clusters in an Australian isolate of Anabaena circinalis and an American isolate of Aphanizomenon sp., both members of the Nostocales. These putative PST gene clusters span approximately 28 kb and contain genes coding for the biosynthesis and export of the toxin. A putative insertion/excision site in the Australian Anabaena circinalis AWQC131C was identified, and the organization and evolution of the gene clusters are discussed. A biosynthetic pathway leading to the formation of saxitoxin and its analogues in these organisms is proposed.

Conclusion
The PST biosynthesis gene cluster presents a mosaic structure, whereby genes have apparently transposed in segments of varying size, resulting in different gene arrangements in all three sxt clusters sequenced so far. The gene cluster organizational structure and sequence similarity seems to reflect the phylogeny of the producer organisms, indicating that the gene clusters have an ancient origin, or that their lateral transfer was also an ancient event. The knowledge we gain from the characterisation of the PST biosynthesis gene clusters, including the identity and sequence of the genes involved in the biosynthesis, may also afford the identification of these gene clusters in dinoflagellates, the cause of human mortalities and significant financial loss to the tourism and shellfish industries.
Gene expression signature of cerebellar hypoplasia in a mouse model of Down syndrome during postnatal development
Authors: Laffaire Julien , Rivals Isabelle , Dauphinot Luce , Pasteau Fabien , Wehrle Rosine , Larrat Benoit , Vitalis Tania , Moldrich Randal X , Rossier Jean , Sinkus Ralph , Herault Yann , Dusart Isabelle , Potier Marie-Claude 
Published: March 2009

AbstractBackgroundDown syndrome is a chromosomal disorder caused by the presence of three copies of chromosome 21. The mechanisms by which this aneuploidy produces the complex and variable phenotype observed in people with Down syndrome are still under discussion. Recent studies have demonstrated an increased transcript level of the three-copy genes with some dosage compensation or amplification for a subset of them. The impact of this gene dosage effect on the whole transcriptome is still debated and longitudinal studies assessing the variability among samples, tissues and developmental stages are needed.ResultsWe thus designed a large scale gene expression study in mice (the Ts1Cje Down syndrome mouse model) in which we could measure the effects of trisomy 21 on a large number of samples (74 in total) in a tissue that is affected in Down syndrome (the cerebellum) and where we could quantify the defect during postnatal development in order to correlate gene expression changes to the phenotype observed. Statistical analysis of microarray data revealed a major gene dosage effect: for the three-copy genes as well as for a 2 Mb segment from mouse chromosome 12 that we show for the first time as being deleted in the Ts1Cje mice. This gene dosage effect impacts moderately on the expression of euploid genes (2.4 to 7.5% differentially expressed). Only 13 genes were significantly dysregulated in Ts1Cje mice at all four postnatal development stages studied from birth to 10 days after birth, and among them are 6 three-copy genes. The decrease in granule cell proliferation demonstrated in newborn Ts1Cje cerebellum was correlated with a major gene dosage effect on the transcriptome in dissected cerebellar external granule cell layer.ConclusionHigh throughput gene expression analysis in the cerebellum of a large number of samples of Ts1Cje and euploid mice has revealed a prevailing gene dosage effect on triplicated genes. Moreover using an enriched cell population that is thought responsible for the cerebellar hypoplasia in Down syndrome, a global destabilization of gene expression was not detected. Altogether these results strongly suggest that the three-copy genes are directly responsible for the phenotype present in cerebellum. We provide here a short list of candidate genes.
Nonlinear modeling of venous leg ulcer healing rates
Authors: Cardinal Matthew , Phillips Tania , Eisenbud David E , Harding Keith , Mansbridge Jonathan , Armstrong David G 
Published: March 2009

Abstract

Background
The purpose of this manuscript was to determine whether the change in wound surface area over time could be described through nonlinear mathematics.

Methods
We studied 3,588 serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized trial of two topical wound treatments.

Results
A majority (72%) of VLUs exhibited surface area reduction via an exponential decay model, particularly during the early stages of healing. These results were consistent with the mechanics of wound contraction and epithelial cell proliferation, supported by the higher frequency at which exponential surface area reduction associated with full wound closure (35% of wounds that fit the exponential model healed vs. 21% of wounds that did not fit the exponential model completely healed during the study period, p = 0.018). Goodness-of-fit statistics suggested that much of the individual variation in healing could be described as nonlinear variation from the exponential model.

Conclusion
We believe that parameter estimates from a mathematical model may provide a more accurate quantification of wound healing rates, and that similar models may someday reach routine use in comparing the efficacy of various treatments in routine practice and in product registration trials.
Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone
Authors: Syversen Unni , Stunes Astrid K , Gustafsson Björn I , Obrant Karl J , Nordsletten Lars , Berge Rolf , Thommesen Liv , Reseland Janne E 
Published: March 2009

Abstract

Background
All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO) and the PPARγ agonist pioglitazone (PIO) on bone in intact female rats.

Methods
Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied.

Results
The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1.

Conclusion
We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation.
Expression of TRPM8 in the distal cerebrospinal fluid-contacting neurons in the brain mesencephalon of rats
Authors: Du Jing , Yang Xinwei , Zhang Licai , Zeng Yin-ming 
Published: March 2009

Abstract

Background
It has been shown that distal cerebrospinal fluid-contacting neurons (dCSF-CNs) exist near the ventral midline of the midbrain aqueduct and also in the grey matter of the inferior third ventricle and the fourth ventricle floor in the superior segment of the pons. The dCSF-CNs communicate between the cerebrospinal fluid (CSF) and the brain parenchyma and may participate in the transduction and regulation of pain signals. The cold sensation receptor channel, TRPM8 is involved in analgesia for neuropathic pain, but whether the TRPM8 receptor exists on dCSF-CNs remains unknown. However, there is preliminary evidence that TRPM8 is expressed in dCSF-CNs and may participate in the transmission and regulation of sensory information between brain parenchyma and cerebrospinal fluid (CSF) in rats.

Methods
Retrograde tracing of the cholera toxin subunit B labeled with horseradish peroxidase (CB-HRP) injected into the lateral ventricle was used to identify dCSF-CNs. A double-labeled immunofluorescent technique and laser scanning confocal microscopy were used to identify the expression of TRPM8 in dCSF-CNs. Software Image-Pro Plus was used to count the number of neurons in three sections where CB-HRP positive neurons were located in the mesencephalon of six rats.

Results
The cell bodies of CB-HRP-positive dCSF-CNs were found in the brain parenchyma near the midline of the ventral Aq, also in the grey of the 3V, and the 4V floor in the superior segment of the pons. In the mesencephalon their processes extended into the CSF. TRPM8 labeled neurons were also found in the same area as were CB-HRP/TRPM8 double-labeled neurons. CB-HRP/TRPM8 double-labeled neurons were found in 42.9 ± 2.3% of neurons labeled by TRPM8, and all CB-HRP-labeled neurons were also labeled with TPRM8.

Conclusion
This study has demonstrated that the cold sensation receptor channel, TRPM8, is localised within the dCSF-CNs of the mesencephalon. TRPM8 acts as receptor of dCSF-CNs for sensation transmission and pain regulation.
The second Symptom Management Research Trial in Oncology (SMaRT Oncology-2): a randomised trial to determine the effectiveness and cost-effectiveness of adding a complex intervention for major depressive disorder to usual care for cancer patients
Authors: Walker Jane , Cassidy Jim , Sharpe Michael ,   the SMaRT Oncology-2 Trialists*
Published: March 2009

Abstract

Background

Depression Care for People with Cancer is a complex intervention delivered by specially trained cancer nurses, under the supervision of a psychiatrist. It is given as a supplement to the usual care for depression, which patients receive from their general practitioner and cancer service. In a 'proof of concept' trial (Symptom Management Research Trials in Oncology-1) Depression Care for People with Cancer improved depression more than usual care alone. The second Symptom Management Research Trial in Oncology (SMaRT Oncology-2 Trial) will test its effectiveness and cost-effectiveness in a 'real world' setting.

Design
A two arm parallel group multi-centre randomised controlled trial.

Trial Procedures
500 patients will be recruited through established systematic Symptom Monitoring Services, which screen patients for depression. Patients will have: a diagnosis of cancer (of various types); an estimated life expectancy of twelve months or more and a diagnosis of Major Depressive Disorder. Patients will be randomised to usual care or usual care plus Depression Care for People with Cancer. Randomisation will be carried out by telephoning a secure computerised central randomisation system or by using a secure web interface. The primary outcome measure is 'treatment response' measured at 24 week outcome data collection. 'Treatment response' will be defined as a reduction of 50% or more in the patient's baseline depression score, measured using the 20-item Symptom Checklist (SCL-20D). Secondary outcomes include remission of major depressive disorder, depression severity and patients' self-rated improvement of depression.

Trial Registration
Current controlled trials ISRCTN40568538

Trial Hypotheses
(1) Depression Care for People with Cancer as a supplement to usual care will be more effective than usual care alone in achieving a 50% reduction in baseline SCL-20D score at 24 weeks. (2) Depression Care for People with Cancer as a supplement to usual care will cost more than usual care alone but will be more cost effective in achieving improvements in patients' depression and quality of life.
A novel and stable "two-hit" acute lung injury model induced by oleic acid in piglets
Authors: Li Xiaofeng , Liu Yinglong , Wang Qiang , Zhu Yaobin , Lv Xiaodong , Liu Jinping 
Published: March 2009

Abstract

Background
Children are susceptible to pulmonary injury, and acute lung injury (ALI) often results in a high mortality and financial cost in pediatric patients. Evidence has showed that oleic acid (OA) plays an important role in ALI. Therefore, it has special significance to study ALI in pediatric patients by using OA-induced animal models. Unfortunately, the animal model hs a high mortality due to hemodynamic instability. The aim of this study was to establish a novel hemodynamically stable OA-induced ALI model in piglets with two hits.

Methods
18 Chinese mini-piglets were randomized into three groups: group C (received saline-ethanol solution), group T (received OA-ethanol solution in routine administration manner) and group H (received OA-ethanol solution in two-hit manner). Hemodynamic and pulmonary function data were measured. Histopathological assessments were performed.

Results
Two piglets in group T died of radical decline of systemic blood pressure. Group T showed more drastic hemodynamic changes than group H especially during the period of 5 to 30 minutes after OA administration. Both Group T and group H all produced severe lung injury, while group C had no significant pathologic changes. OA-induced hypotension might be caused by pulmonary hypertension rather than comprised left ventricular function.

Conclusion
OA leads to severe pulmonary hypertension which results in hemodynamic fluctuation in OA-induced ALI model. It is the first report on hemodynamic stable ALI animal model in piglets using two-hit method. The two-hit ALI animal model fulfils the ALI criteria and has the following characteristics: hemodynamic stability, stable damage to gas exchange and comparability with pediatric patients in body weight and corresponding age. The two-hit ALI animal model can be used to study the basic mechanism and the therapeutic strategies for pediatric ALI.
Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation
Authors: Inoue Naoko , Nakao Harumi , Migishima Rika , Hino Toshiaki , Matsui Minoru , Hayashi Fumihiko , Nakao Kazuki , Manabe Toshiya , Aiba Atsu , Inokuchi Kaoru 
Published: March 2009

Abstract

Background
The formation of long-term memory (LTM) and the late phase of long-term potentiation (L-LTP) depend on macromolecule synthesis, translation, and transcription in neurons. vesl-1S (V ASP/E na-related gene upregulated during s eizure and L TP, also known as homer-1a) is an LTP-induced immediate early gene. The short form of Vesl (Vesl-1S) is an alternatively spliced isoform of the vesl-1 gene, which also encodes the long form of the Vesl protein (Vesl-1L). Vesl-1L is a postsynaptic scaffolding protein that binds to and modulates the metabotropic glutamate receptor 1/5 (mGluR1/5), the IP3 receptor, and the ryanodine receptor. Vesl-1 null mutant mice show abnormal behavior, which includes anxiety- and depression-related behaviors, and an increase in cocaine-induced locomotion; however, the function of the short form of Vesl in behavior is poorly understood because of the lack of short-form-specific knockout mice.

Results
In this study, we generated short-form-specific gene targeting (KO) mice by knocking in part of vesl-1L/homer-1c cDNA. Homozygous KO mice exhibited normal spine number and morphology. Using the contextual fear conditioning test, we demonstrated that memory acquisition and short-term memory were normal in homozygous KO mice. In contrast, these mice showed impairment in fear memory consolidation. Furthermore, the process from recent to remote memory was affected in homozygous KO mice. Interestingly, reactivation of previously consolidated fear memory attenuated the conditioning-induced freezing response in homozygous KO mice, which suggests that the short form plays a role in fear memory reconsolidation. General activity, emotional performance, and sensitivity to electrofootshock were normal in homozygous KO mice.

Conclusion
These results indicate that the short form of the Vesl family of proteins plays a role in multiple steps of long-term, but not short-term, fear memory formation.
Brain serotonin transporter binding in former users of MDMA (‘ecstasy’)
Authors: Selvaraj Sudhakar , Hoshi Rosa , Bhagwagar Zubin , Murthy Naga Venkatesha , Hinz Rainer , Cowen Philip , Curran H. Valerie , Grasby Paul 
Published: March 2009

BackgroundAnimal experimental studies have prompted concerns that widespread use of 3,4-methylenedioxymethamphetamine (MDMA; ‘ecstasy’) by young people may pose a major public health problem in terms of persistent serotonin neurotoxicity.AimsTo determine the status of brain serotonin neurons in a group of abstinent MDMA users.MethodWe assessed the integrity of brain serotonin neurons by measuring serotonin transporter (SERT) binding using positron emission tomography (PET) and [11C]DASB in 12 former MDMA users, 9 polydrug users who had never taken MDMA and 19 controls who reported no history of illicit drug use.ResultsThere was no significant difference in the binding potential of [11C]DASB between the groups in any of the brain regions examined.ConclusionsTo the extent that [11C]DASB binding provides an index of the integrity of serotonin neurons, our findings suggest that MDMA use may not result in long-term damage to serotonin neurons when used recreationally in humans.
Phase II Evaluation of Pemetrexed in the Treatment of Recurrent or Persistent Platinum-Resistant Ovarian or Primary Peritoneal Carcinoma: A Study of the Gynecologic Oncology Group
Authors: Miller David S. , Blessing John A. , Krasner Carolyn N. , Mannel Robert S. , Hanjani Parviz , Pearl Michael L. , Waggoner Steven E. , Boardman Cecelia H. 
Published: March 2009

Purpose To estimate the antitumor activity of pemetrexed in patients with persistent or recurrent platinum-resistant epithelial ovarian or primary peritoneal cancer and to determine the nature and degree of toxicities. Patients and Methods A phase II trial was conducted by the Gynecologic Oncology Group. Patients must have had cancer that had progressed on platinum-based primary chemotherapy or recurred within 6 months. Pemetrexed at a dose of 900 mg/m2 was to be administered as an intravenous infusion over 10 minutes every 21 days. Dose delay and adjustment was permitted for toxicity. Treatment was continued until disease progression or unacceptable adverse effects. Results From July 6, 2004, to August 23, 2006, 51 patients were entered. A total of 259 cycles (median, four; range one to 19 cycles) of pemetrexed were administered, with 40% of patients receiving six or more cycles. Overall, the treatment was well tolerated. More serious toxicities (grade 3 and 4) included neutropenia in 42%, leukopenia in 25%, anemia in 15%, and constitutional in 15% of patients. No treatment-related deaths were reported. One patient (2%) had a complete and nine patients (19%) had partial responses, with a median duration response of 8.4 months. Seventeen patients (35%) had stable disease for a median of 4.1 months. Eighteen patients (38%) had increasing disease. Three patients (6%) were not assessable. Median progression-free survival was 2.9 months, and overall survival was 11.4 months. Conclusion Pemetrexed has sufficient activity in the treatment of recurrent platinum-resistant ovarian cancer at the dose and schedule tested to warrant further investigation.