bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pergolide Is an Inhibitor of Voltage-Gated Potassium Channels, Including Kv1.5, and Causes Pulmonary Vasoconstriction
Authors: Hong Zhigang , Smith Andrew J. , Archer Stephen L. , Wu Xi-Chen , Nelson Daniel P. , Peterson Douglas , Johnson Gerhard , Weir E. Kenneth 
Published: August 2005

Background—Pergolide produces clinical benefit in Parkinson disease by stimulating dopamine D1and D2receptors. An increased incidence of carcinoid-like heart valve disease (CLHVD) has been noted in pergolide users, reminiscent of that induced by certain anorexigens used for weight reduction. Anorexigens that modulate serotonin release and reuptake, such as dexfenfluramine, were withdrawn from sale because of CLHVD. Interestingly, the anorexigens also caused pulmonary arterial hypertension (PAH). Anorexigens were shown to enhance hypoxic pulmonary vasoconstriction, in part by inhibiting voltage-gated K+channels (Kv) in pulmonary artery smooth muscle cells (PASMCs). Although PAH has not been associated with pergolide use, we hypothesized that pergolide might have similar effects on hypoxic pulmonary vasoconstriction and Kv channels.Methods and Results—Pergolide enhanced hypoxic pulmonary vasoconstriction in the isolated perfused rat lung compared with control lungs (mean pulmonary artery pressure 32±3 versus 21±2 mm Hg;P<0.01). Pergolide also caused vasoconstriction in rat pulmonary artery rings. Pergolide inhibited PASMC potassium current density, resulting in membrane depolarization (from −51±2 to −44±1 mV) and increased cytosolic calcium in both rat and human PASMCs. Pergolide directly inhibited heterologously expressed Kv1.5 and KCachannels.Conclusions—Pergolide causes Kv channel inhibition and, despite being from a different class of drugs, has pulmonary vascular effects reminiscent of dexfenfluramine. Coupled with their shared proclivity to induce CLHVD, these findings suggest that clinical monitoring for pergolide-induced PAH should be considered.
Hypoxia-activated genes from early placenta are elevated in Preeclampsia, but not in Intra-Uterine Growth Retardation
Authors: Vaiman Daniel , Mondon Françoise , Garcès-Duran Alexandra , Mignot Thérèse-Marie , Robert Brigitte , Rebourcet Régis , Jammes Hélène , Chelbi Sonia T , Quetin Frédérique , Marceau Geoffrey , Sapin Vincent , Piumi François , Danan Jean-Louis , Rigourd Virginie , Carbonne Bruno , Ferré Françoise 
Published: August 2005

AbstractBackgroundAs a first step to explore the possible relationships existing between the effects of low oxygen pressure in the first trimester placenta and placental pathologies developing from mid-gestation, two subtracted libraries totaling 2304 cDNA clones were constructed. For achieving this, two reciprocal suppressive/subtractive hybridization procedures (SSH) were applied to early (11 weeks) human placental villi after incubation either in normoxic or in hypoxic conditions. The clones from both libraries (1440 hypoxia-specific and 864 normoxia-specific) were spotted on nylon macroarrays. Complex cDNAs probes prepared from placental villi (either from early pregnancy, after hypoxic or normoxic culture conditions, or near term for controls or pathological placentas) were hybridized to the membranes.ResultsThree hundred and fifty nine clones presenting a hybridization signal above the background were sequenced and shown to correspond to 276 different genes. Nine of these genes are mitochondrial, while 267 are nuclear. Specific expression profiles characteristic of preeclampsia (PE) could be identified, as well as profiles specific of intra-uterine growth retardation (IUGR).Focusing on the chromosomal distribution of the fraction of genes that responded in at least one hybridization experiment, we could observe a highly significant chromosomal clustering of 54 genes into 8 chromosomal regions, four of which containing imprinted genes. Comparative mapping data indicate that these imprinted clusters are maintained in synteny in mice, and apparently in cattle and pigs, suggesting that the maintenance of such syntenies is requested for achieving a normal placental physiology in eutherian mammals.ConclusionWe could demonstrate that genes induced in PE were also genes highly expressed under hypoxic conditions (P = 5.10-5), which was not the case for isolated IUGR. Highly expressed placental genes may be in syntenies conserved interspecifically, suggesting that the maintenance of such clusters is requested for achieving a normal placental physiology in eutherian mammals.
GH97 is a new family of glycoside hydrolases, which is related to the α-galactosidase superfamily
Authors: Naumoff Daniil G 
Published: August 2005

Abstract

Background
As a rule, about 1% of genes in a given genome encode glycoside hydrolases and their homologues. On the basis of sequence similarity they have been grouped into more than ninety GH families during the last 15 years. The GH97 family has been established very recently and initially included only 18 bacterial proteins. However, the evolutionary relationship of the genes encoding proteins of this family remains unclear, as well as their distribution among main groups of the living organisms.

Results
The extensive search of the current databases allowed us to double the number of GH97 family proteins. Five subfamilies were distinguished on the basis of pairwise sequence comparison and phylogenetic analysis. Iterative sequence analysis revealed the relationship of the GH97 family with the GH27, GH31, and GH36 families of glycosidases, which belong to the α-galactosidase superfamily, as well as a more distant relationship with some other glycosidase families (GH13 and GH20).

Conclusion
The results of this study show an unexpected sequence similarity of GH97 family proteins with glycoside hydrolases from several other families, that have (β/α)8-barrel fold of the catalytic domain and a retaining mechanism of the glycoside bond hydrolysis. These data suggest a common evolutionary origin of glycosidases representing different families and clans.
Epidermal growth factor (EGF) withdrawal masks gene expression differences in the study of pituitary adenylate cyclase-activating polypeptide (PACAP) activation of primary neural stem cell proliferation
Authors: Sievertzon Maria , Wirta Valtteri , Mercer Alex , Frisén Jonas , Lundeberg Joakim 
Published: August 2005

Abstract

Background
The recently discovered adult neural stem cells, which maintain continuous generation of new neuronal and glial cells throughout adulthood, are a promising and expandable source of cells for use in cell replacement therapies within the central nervous system. These cells could either be induced to proliferate and differentiate endogenously, or expanded and differentiated in culture before being transplanted into the damaged site of the brain. In order to achieve these goals effective strategies to isolate, expand and differentiate neural stem cells into the desired specific phenotypes must be developed. However, little is known as yet about the factors and mechanisms influencing these processes. It has recently been reported that pituitary adenylate cyclase-activating polypeptide (PACAP) promotes neural stem cell proliferation both in vivo and in vitro.

Results
We used cDNA microarrays with the aim of analysing the transcriptional changes underlying PACAP induced proliferation of neural stem cells. The primary neural stem/progenitor cells used were neurospheres, generated from the lateral ventricle wall of the adult mouse brain. The results were compared to both differentiation and proliferation controls, which revealed an unexpected and significant differential expression relating to withdrawal of epidermal growth factor (EGF) from the neurosphere growth medium. The effect of EGF removal was so pronounced that it masked the changes in gene expression patterns produced by the addition of PACAP.

Conclusion
Experimental models aiming at transcriptional analysis of induced proliferation in primary neural stem cells need to take into consideration the significant effect on transcription caused by removal of EGF. Alternatively, EGF-free culture conditions need to be developed.
The cost-effectiveness of early noninvasive ventilation for ALS patients
Authors: Gruis Kirsten L , Chernew Michael E , Brown Devin L 
Published: August 2005

AbstractBackgroundOptimal timing of noninvasive positive pressure ventilation (NIPPV) initiation in patients with amyotrophic lateral sclerosis (ALS) is unknown, but NIPPV appears to benefit ALS patients who are symptomatic from pulmonary insufficiency. This has prompted research proposals of earlier NIPPV initiation in the ALS disease course in an attempt to further improve ALS patient quality of life and perhaps survival. We therefore used a cost-utility analysis to determine a priori what magnitude of health-related quality of life (HRQL) improvement early NIPPV initiation would need to achieve to be cost-effective in a future clinical trial.MethodsUsing a Markov decision analytic model we calculated the benefit in health-state utility that NIPPV initiated at ALS diagnosis must achieve to be cost-effective. The primary outcome was the percent utility gained through NIPPV in relation to two common willingness-to-pay thresholds: $50,000 and $100,000 per quality-adjusted life year (QALY).ResultsOur results indicate that if NIPPV begun at the time of diagnosis improves ALS patient HRQL as little as 13.5%, it would be a cost-effective treatment. Tolerance of NIPPV (assuming a 20% improvement in HRQL) would only need to exceed 18% in our model for treatment to remain cost-effective using a conservative willingness-to-pay threshold of $50,000 per QALY.ConclusionIf early use of NIPPV in ALS patients is shown to improve HRQL in future studies, it is likely to be a cost-effective treatment. Clinical trials of NIPPV begun at the time of ALS diagnosis are therefore warranted from a cost-effectiveness standpoint.
Hazardous waste sites and stroke in New York State
Authors: Shcherbatykh Ivan , Huang Xiaoyu , Lessner Lawrence , Carpenter David O 
Published: August 2005

Abstract

Background -
Environmental exposure to persistent organic pollutants (POPs) may lead to elevation of serum lipids, increasing risk of atherosclerosis with thromboembolism, a recognized cause of stroke. We tested the hypothesis that exposure to contaminants from residence near hazardous waste sites in New York State influences the occurrence of stroke.

Methods -
The rates of stroke hospital discharges were compared among residents of zip codes containing hazardous waste sites with POPs, other pollutants or without any waste sites using information for 1993–2000 from the New York Statewide Planning and Research Cooperative System (SPARCS) database, containing the records of all discharge diagnoses for patients admitted to state-regulated hospitals.

Results -
After adjustment for age and race, the hospitalization rate for stroke in zip codes with POPs-contaminated sites was 15% higher than in zip codes without any documented hazardous waste sites (RR 1.15, 95% CI, 1.05, 1.26). For ischemic stroke only, the RR was 1.17 (95% CI 1.04, 1.31). Residents of zip codes containing other waste sites showed a RR of 1.13 (95% CI, 1.02, 1.24) as compared to zip codes without an identified waste site.

Conclusion -
These results suggest that living near a source of POPs contamination constitutes a risk of exposure and an increased risk of acquiring cerebrovascular disease. However further research with better control of individual risk factors and direct measurement of exposure is necessary for providing additional support for this hypothesis.
Unsatisfactory gene transfer into bone-resorbing osteoclasts with liposomal transfection systems
Authors: Laitala-Leinonen Tiina 
Published: August 2005

Abstract

Background
Bone-resorbing osteoclasts are multinucleated cells that are formed via fusion of their hematopoietic stem cells. Many of the details of osteoclast formation, activation and motility remain unsolved. Therefore, there is an interest among bone biologists to transfect the terminally differentiated osteoclasts and follow their responses to the transgenes in vitro. Severe difficulties in transfecting the large, adherent osteoclasts have been encountered, however, making the use of modern cell biology tools in osteoclast research challenging. Transfection of mature osteoclasts by non-viral gene transfer systems has not been reported.

Results
We have systematically screened the usefulness of several commercial DNA transfection systems in human osteoclasts and their mononuclear precursor cell cultures, and compared transfection efficacy to adenoviral DNA transfection. None of the liposome-based or endosome disruption-inducing systems could induce EGFP-actin expression in terminally differentiated osteoclasts. Instead, a massive cell death by apoptosis was found with all concentrations and liposome/DNA-ratios tested. Best transfection efficiencies were obtained by adenoviral gene delivery. Marginal DNA transfection was obtained by just adding the DNA to the cell culture medium. When bone marrow-derived CD34-positive precursor cells were transfected, some GFP-expression was found at the latest 24 h after transfection. Large numbers of apoptotic cells were found and those cells that remained alive, failed to form osteoclasts when cultured in the presence of RANKL and M-CSF, key regulators of osteoclast formation. In comparison, adenoviral gene delivery resulted in the transfection of CD34-positive cells that remained GFP-positive for up to 5 days and allowed osteoclast formation.

Conclusion
Osteoclasts and their precursors are sensitive to liposomal transfection systems, which induce osteoclast apoptosis. Gene transfer to mononuclear osteoclast precursors or differentiated osteoclasts was not possible with any of the commercial transfection systems tested. Osteoclasts are non-dividing, adherent cells that are difficult to grow as confluent cultures, which may explain problems with transfection reagents. Large numbers of αvβ3 integrin on the osteoclast surface allows adenovirus endocytosis and infection proceeds in dividing and non-dividing cells efficiently. Viral gene delivery is therefore currently the method of choice for osteoclast transfection.
Health related quality of life in sickle cell patients: The PiSCES project
Authors: McClish Donna K , Penberthy Lynne T , Bovbjerg Viktor E , Roberts John D , Aisiku Imoigele P , Levenson James L , Roseff Susan D , Smith Wally R 
Published: August 2005

Abstract

Background
Sickle cell disease (SCD) is a chronic disease associated with high degrees of morbidity and increased mortality. Health-related quality of life (HRQOL) among adults with sickle cell disease has not been widely reported.

Methods
We administered the Medical Outcomes Study 36-item Short-Form to 308 patients in the Pain in Sickle Cell Epidemiology Study (PiSCES) to assess HRQOL. Scales included physical function, physical and emotional role function, bodily pain, vitality, social function, mental health, and general health. We compared scores with national norms using t-tests, and with three chronic disease cohorts: asthma, cystic fibrosis and hemodialysis patients using analysis of variance and Dunnett's test for comparison with a control. We also assessed whether SCD specific variables (genotype, pain, crisis and utilization) were independently predictive of SF-36 subscales, controlling for socio-demographic variables using regression.

Results
Patients with SCD scored significantly worse than national norms on all subscales except mental health. Patients with SCD had lower HRQOL than cystic fibrosis patients except for mental health. Scores were similar for physical function, role function and mental health as compared to asthma patients, but worse for bodily pain, vitality, social function and general health subscales. Compared to dialysis patients, sickle cell disease patients scored similarly on physical role and emotional role function, social functioning and mental health, worse on bodily pain, general health and vitality and better on physical functioning. Surprisingly, genotype did not influence HRQOL except for vitality. However, scores significantly decreased as pain levels increased.

Conclusion
SCD patients experience health related quality of life worse than the general population, and in general, their scores were most similar to patients undergoing hemodialysis. Practitioners should regard their HRQOL as severely compromised. Interventions in SCD should consider improvements in health related quality of life as important outcomes.
Exogenous estradiol enhances apoptosis in regressing post-partum rat corpora lutea possibly mediated by prolactin
Authors: Goyeneche Alicia A , Telleria Carlos M 
Published: August 2005

Abstract

Background
In pregnant rats, structural luteal regression takes place after parturition and is associated with cell death by apoptosis. We have recently shown that the hormonal environment is responsible for the fate of the corpora lutea (CL). Changing the levels of circulating hormones in post-partum rats, either by injecting androgen, progesterone, or by allowing dams to suckle, was coupled with a delay in the onset of apoptosis in the CL. The objectives of the present investigation were: i) to examine the effect of exogenous estradiol on apoptosis of the rat CL during post-partum luteal regression; and ii) to evaluate the post-partum luteal expression of the estrogen receptor (ER) genes.

Methods
In a first experiment, rats after parturition were separated from their pups and injected daily with vehicle or estradiol benzoate for 4 days. On day 4 post-partum, animals were sacrificed, blood samples were taken to determine serum concentrations of hormones, and the ovaries were isolated to study apoptosis in situ. In a second experiment, non-lactating rats after parturition received vehicle, estradiol benzoate or estradiol benzoate plus bromoergocryptine for 4 days, and their CL were isolated and used to study apoptosis ex vivo. In a third experiment, we obtained CL from rats on day 15 of pregnancy and from non-lactating rats on day 4 post-partum, and studied the expression of the messenger RNAs (mRNAs) encoding the ERalpha and ERbeta genes.

Results
Exogenous administration of estradiol benzoate induced an increase in the number of apoptotic cells within the CL on day 4 post-partum when compared with animals receiving vehicle alone. Animals treated with the estrogen had higher serum prolactin and progesterone concentrations, with no changes in serum androstenedione. Administration of bromoergocryptine blocked the increase in serum prolactin and progesterone concentrations, and DNA fragmentation induced by the estrogen treatment. ERalpha and ERbeta mRNAs were expressed in CL of day 4 post-partum animals at levels similar to those found in CL of day 15 pregnant animals.

Conclusion
We have established that estradiol accelerates apoptosis in the CL during post-partum luteal regression through a mechanism that possibly involves the secretion of pituitary prolactin. We have also shown that the post-partum rat CL express ERalpha and ERbeta mRNAs suggesting that they can be targeted by estrogen.
Peroxisome proliferator-activated receptors (PPARs) and ovarian function – implications for regulating steroidogenesis, differentiation, and tissue remodeling
Authors: Komar Carolyn M 
Published: August 2005

Abstract
The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors involved in varied and diverse processes such as steroidogenesis, angiogenesis, tissue remodeling, cell cycle, apoptosis, and lipid metabolism. These processes are critical for normal ovarian function, and all three PPAR family members – alpha, delta, and gamma, are expressed in the ovary. Most notably, the expression of PPARgamma is limited primarily to granulosa cells in developing follicles, and is regulated by luteinizing hormone (LH). Although much has been learned about the PPARs since their initial discovery, very little is known regarding their function in ovarian tissue. This review highlights what is known about the roles of PPARs in ovarian cells, and discusses potential mechanisms by which PPARs could influence ovarian function. Because PPARs are activated by drugs currently in clinical use (fibrates and thiazolidinediones), it is important to understand their role in the ovary, and how manipulation of their activity may impact ovarian physiology as well as ovarian pathology.
The unsuitability of html-based colour charts for estimating animal colours – a comment on Berggren and Merilä (2004)
Authors: Stevens Martin , Cuthill Innes C 
Published: August 2005

Abstract

Background
A variety of techniques are used to study the colours of animal signals, including the use of visual matching to colour charts. This paper aims to highlight why they are generally an unsatisfactory tool for the measurement and classification of animal colours and why colour codes based on HTML (really RGB) standards, as advocated in a recent paper, are particularly inappropriate. There are many theoretical arguments against the use of colour charts, not least that human colour vision differs markedly from that of most other animals. However, the focus of this paper is the concern that, even when applied to humans, there is no simple 1:1 mapping from an RGB colour space to the perceived colours in a chart (the results are both printer- and illumination-dependent). We support our criticisms with data from colour matching experiments with humans, involving self-made, printed colour charts.

Results
Colour matching experiments with printed charts involving 11 subjects showed that the choices made by individuals were significantly different between charts that had exactly the same RGB values, but were produced from different printers. Furthermore, individual matches tended to vary under different lighting conditions. Spectrophotometry of the colour charts showed that the reflectance spectra of the charts varied greatly between printers and that equal steps in RGB space were often far from equal in terms of reflectance on the printed charts.

Conclusion
In addition to outlining theoretical criticisms of the use of colour charts, our empirical results show that: individuals vary in their perception of colours, that different printers produce strikingly different results when reproducing what should be the same chart, and that the characteristics of the light irradiating the surface do affect colour perception. Therefore, we urge great caution in the use of colour charts to study animal colour signals. They should be used only as a last resort and in full knowledge of their limitations, with specially produced charts made to high industry standards.