bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of genes differentially expressed in T cells following stimulation with the chemokines CXCL12 and CXCL10
Authors: Nagel JE , Smith RJ , Shaw L , Bertak D , Dixit VD , Schaffer EM , Taub DD 
Published: August 2004

Abstract
Background
Chemokines are involved in many biological activities ranging from leukocyte differentiation to neuronal morphogenesis. Despite numerous reports describing chemokine function, little is known about the molecular changes induced by cytokines.

Methods
We have isolated and identified by differential display analysis 182 differentially expressed cDNAs from CXCR3-transfected Jurkat T cells following treatment with CXCL12 or CXCL10. These chemokine-modulated genes were further verified using quantitative RT-PCR and Western blot analysis.

Results
One hundred and forty-six of the cDNAs were successfully cloned, sequenced, and identified by BLAST. Following removal of redundant and non-informative clones, seventeen mRNAs were found to be differentially expressed post treatment with either chemokine ligand with several representing known genes with established functions. Twenty-one genes were upregulated in these transfected Jurkat cells following both CXCL12 and CXCL10, four genes displayed a discordant response and seven genes were downregulated upon treatment with either chemokine. Identified genes include geminin (GEM), thioredoxin (TXN), DEAD/H box polypeptide 1 (DDX1), growth hormone inducible transmembrane protein (GHITM), and transcription elongation regulator 1 (TCERG1). Subsequent analysis of several of these genes using semi-quantitative PCR and western blot analysis confirmed their differential expression post ligand treatment.

Conclusions
Together, these results provide insight into chemokine-induced gene activation and identify potentially novel functions for known genes in chemokine biology.
The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner
Authors: Wilson Brian J , Bates Gaynor J , Nicol Samantha M , Gregory David J , Perkins Neil D , Fuller-Pace Frances V 
Published: August 2004

Abstract
Background
p68 (Ddx5) and p72 (Ddx17) are highly related members of the DEAD box family and are established RNA helicases. They have been implicated in growth regulation and have been shown to be involved in both pre-mRNA and pre-rRNA processing. More recently, however, these proteins have been reported to act as transcriptional co-activators for estrogen-receptor alpha (ERα). Furthermore these proteins were shown to interact with co-activators p300/CBP and the RNA polymerase II holoenzyme. Taken together these reports suggest a role for p68 and p72 in transcriptional activation.

Results
In this report we show that p68 and p72 can, in some contexts, act as transcriptional repressors. Targeting of p68 or p72 to constitutive promoters leads to repression of transcription; this repression is promoter-specific. Moreover both p68 and p72 associate with histone deacetylase 1 (HDAC1), a well-established transcriptional repression protein.

Conclusions
It is therefore clear that p68 and p72 are important transcriptional regulators, functioning as co-activators and/or co-repressors depending on the context of the promoter and the transcriptional complex in which they exist.
3 dimensional modelling of early human brain development using optical projection tomography
Authors: Kerwin Janet , Scott Mark , Sharpe James , Puelles Luis , Robson Stephen C , Martínez-de-la-Torre Margaret , Ferran Jose Luis , Feng Guangjie , Baldock Richard , Strachan Tom , Davidson Duncan , Lindsay Susan 
Published: August 2004

Abstract
Background
As development proceeds the human embryo attains an ever more complex three dimensional (3D) structure. Analyzing the gene expression patterns that underlie these changes and interpreting their significance depends on identifying the anatomical structures to which they map and following these patterns in developing 3D structures over time. The difficulty of this task greatly increases as more gene expression patterns are added, particularly in organs with complex 3D structures such as the brain. Optical Projection Tomography (OPT) is a new technology which has been developed for rapidly generating digital 3D models of intact specimens. We have assessed the resolution of unstained neuronal structures within a Carnegie Stage (CS)17 OPT model and tested its use as a framework onto which anatomical structures can be defined and gene expression data mapped.

Results
Resolution of the OPT models was assessed by comparison of digital sections with physical sections stained, either with haematoxylin and eosin (H&E) or by immunocytochemistry for GAP43 or PAX6, to identify specific anatomical features. Despite the 3D models being of unstained tissue, peripheral nervous system structures from the trigeminal ganglion (~300 μm by ~150 μm) to the rootlets of cranial nerve XII (~20 μm in diameter) were clearly identifiable, as were structures in the developing neural tube such as the zona limitans intrathalamica (core is ~30 μm thick). Fourteen anatomical domains have been identified and visualised within the CS17 model. Two 3D gene expression domains, known to be defined by Pax6 expression in the mouse, were clearly visible when PAX6 data from 2D sections were mapped to the CS17 model. The feasibility of applying the OPT technology to all stages from CS12 to CS23, which encompasses the major period of organogenesis for the human developing central nervous system, was successfully demonstrated.

Conclusion
In the CS17 model considerable detail is visible within the developing nervous system at a minimum resolution of ~20 μm and 3D anatomical and gene expression domains can be defined and visualised successfully. The OPT models and accompanying technologies for manipulating them provide a powerful approach to visualising and analysing gene expression and morphology during early human brain development.
A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats
Authors: McClelland David , Evans Rhian M , Barkworth Louise , Martin Duncan J , Scott Roderick H 
Published: August 2004

Abstract
Background
Gabapentin and pregabalin have wide-ranging therapeutic actions, and are structurally related to the inhibitory neurotransmitter GABA. Gabapentin, pregablin and GABA can all modulate voltage-activated Ca2+ channels. In this study we have used whole cell patch clamp recording and fura-2 Ca2+ imaging to characterise the actions of pregabalin on the electrophysiological properties of cultured dorsal root ganglion (DRG) neurones from neonatal rats. The aims of this study were to determine whether pregabalin and gabapentin had additive inhibitory effects on high voltage-activated Ca2+ channels, evaluate whether the actions of pregabalin were dependent on GABA receptors and characterise the actions of pregabalin on voltage-activated potassium currents.

Results
Pregabalin (25 nM – 2.5 μM) inhibited 20–30% of the high voltage-activated Ca2+ current in cultured DRG neurones. The residual Ca2+ current recorded in the presence of pregabalin was sensitive to the L-type Ca2+ channel modulator, Bay K8644. Saturating concentrations of gabapentin failed to have additive effects when applied with pregabalin, indicating that these two compounds act on the same type(s) of voltage-activated Ca2+ channels but the majority of Ca2+ current was resistant to both drugs. The continual application of GABA, the GABAB receptor antagonist CGP52432, or intracellular photorelease of GTP-γ-S had no effect on pregabalin-induced inhibition of Ca2+ currents. Although clear inhibition of Ca2+ influx was produced by pregabalin in a population of small neurones, a significant population of larger neurones showed enhanced Ca2+ influx in response to pregabalin. The enhanced Ca2+ influx evoked by pregabalin was mimicked by partial block of K+ conductances with tetraethylammonium.
Pregabalin produced biphasic effects on voltage-activated K+ currents, the inhibitory effect of pregabalin was prevented with apamin. The delayed enhancement of K+ currents was attenuated by pertussis toxin and by intracellular application of a (Rp)-analogue of cAMP.

Conclusions
Pregabalin reduces excitatory properties of cultured DRG neurones by modulating voltage-activated Ca2+ and K+ channels. The pharmacological activity of pregabalin is similar but not identical to that of gabapentin. The actions of pregabalin may involve both extracellular and intracellular drug target sites and modulation of a variety of neuronal conductances, by direct interactions, and through intracellular signalling involving protein kinase A.
Proteasome inhibitors: Their effects on arachidonic acid release from cells in culture and arachidonic acid metabolism in rat liver cells
Authors: Levine Lawrence 
Published: August 2004

Abstract
Background
I have postulated that arachidonic acid release from rat liver cells is associated with cancer chemoprevention. Since it has been reported that inhibition of proteasome activities may prevent cancer, the effects of proteasome inhibitors on arachidonic acid release from cells and on prostaglandin I2 production in rat liver cells were studied.

Results
The proteasome inhibitors, epoxomicin, lactacystin and carbobenzoxy-leucyl-leucyl-leucinal, stimulate the release of arachidonic acid from rat glial, human colon carcinoma, human breast carcinoma and the rat liver cells. They also stimulate basal and induced prostacycin production in the rat liver cells. The stimulated arachidonic acid release and basal prostaglandin I2 production in rat liver cells is inhibited by actinomycin D.

Conclusions
Stimulation of arachidonic acid release and arachidonic acid metabolism may be associated with some of the biologic effects observed after proteasome inhibition, e.g. prevention of tumor growth, induction of apoptosis, stimulation of bone formation.
Publication bias in situ
Authors: Phillips Carl V 
Published: August 2004

Abstract
Background
Publication bias, as typically defined, refers to the decreased likelihood of studies' results being published when they are near the null, not statistically significant, or otherwise "less interesting." But choices about how to analyze the data and which results to report create a publication bias within the published results, a bias I label "publication bias in situ" (PBIS).

Discussion
PBIS may create much greater bias in the literature than traditionally defined publication bias (the failure to publish any result from a study). The causes of PBIS are well known, consisting of various decisions about reporting that are influenced by the data. But its impact is not generally appreciated, and very little attention is devoted to it. What attention there is consists largely of rules for statistical analysis that are impractical and do not actually reduce the bias in reported estimates. PBIS cannot be reduced by statistical tools because it is not fundamentally a problem of statistics, but rather of non-statistical choices and plain language interpretations. PBIS should be recognized as a phenomenon worthy of study – it is extremely common and probably has a huge impact on results reported in the literature – and there should be greater systematic efforts to identify and reduce it. The paper presents examples, including results of a recent HIV vaccine trial, that show how easily PBIS can have a large impact on reported results, as well as how there can be no simple answer to it.

Summary
PBIS is a major problem, worthy of substantially more attention than it receives. There are ways to reduce the bias, but they are very seldom employed because they are largely unrecognized.
Nitric oxide-an endogenous inhibitor of gastric acid secretion in isolated human gastric glands
Authors: Berg Anna , Redeen Stefan , Ericson Ann-Charlott , Sjöstrand Sven Erik 
Published: August 2004

Abstract
Background
Endothelial nitric oxide synthase (eNOS) has previously been detected in the glandular part of the human gastric mucosa. Furthermore, nitric oxide (NO) has been shown to influence gastric secretion in various animal models. The present study was conducted to investigate the influence of exogenously and endogenously derived NO on histamine- and cAMP-stimulated gastric acid secretion in isolated human oxyntic glands.

Methods
Oxyntic glands were isolated from human gastric biopsies and were subsequently pre-treated with NO donors and nitric oxide synthase inhibitors and then exposed to histamine or dibutyryl-cAMP (db-cAMP). The secretory response of the glands was determined as accumulation of [14C]aminopyrine.

Results
The histamine- or db-cAMP-induced acid secretion was attenuated by L-arginine, a known source of endogenous NO, and also by the NO-donors sodium nitroprusside (SNP) and S-nitroso-N-acetyl-penicillamine (SNAP). Pre-treatment with either of the NOS inhibitors NG-nitro-L-arginine methyl ester (L-NAME) or NG-nitro-L-arginine (L-NNA) enhanced the secretory response.

Conclusion
Our results show that NO inhibits gastric acid secretion in isolated human gastric glands, and that there is endogenous formation of NO within the glandular epithelium in the vicinity of the parietal cells.
Meningitis due to Fusobacterium necrophorumin an adult
Authors: Garimella SreeNeelima , Inaparthy Aparna , Herchline Thomas 
Published: August 2004

Abstract
Background
Fusobacterium necrophorum may cause a number of clinical syndromes, collectively known as necrobacillosis. Meningitis is a significant cause of mortality, rarely reported in the adult population.

Case presentation
We report a fatal case of meningitis, caused by Fusobacterium necrophorum, secondary to otitis media in an alcoholic male. Diagnosis was delayed due to the typical slow growth of the organism. The clinical course was complicated by encephalitis and by hydrocephalus. The patient failed to respond to metronidazole and penicillin. The patient died on day 12 from increased intracranial pressure and brain stem infarction.

Conclusions
This case emphasizes the need for a high index of clinical suspicion to make the diagnosis of Fusobacterium necrophorum meningitis. We recommend the use of appropriate anaerobic culture techniques and antimicrobial coverage for anaerobic organisms when the gram stain shows gram negative bacilli.
Misoprostol for treating postpartum haemorrhage: a randomized controlled trial [ISRCTN72263357]
Authors: Hofmeyr G Justus , Ferreira Sandra , Nikodem V Cheryl , Mangesi Lindeka , Singata Mandisa , Jafta Zukiswa , Maholwana Babalwa , Mlokoti Zonke , Walraven Gijs , Gülmezoglu A Metin 
Published: August 2004

Abstract
Background
Postpartum haemorrhage remains an important cause of maternal death despite treatment with conventional therapy. Uncontrolled studies and one randomised comparison with conventional oxytocics have reported dramatic effects with high-dose misoprostol, usually given rectally, for treatment of postpartum haemorrhage, but this has not been evaluated in a placebo-controlled trial.

Methods
The study was conducted at East London Hospital Complex, Tembisa and Chris Hani Baragwanath Hospitals, South Africa. Routine active management of the third stage of labour was practised. Women with more than usual postpartum bleeding thought to be related to inadequate uterine contraction were invited to participate, and to sign informed consent. All routine treatment was given from a special 'Postpartum Haemorrhage Trolley'. In addition, participants who consented were enrolled by drawing the next in a series of randomised treatment packs containing either misoprostol 5 × 200 μg or similar placebo, which were given 1 orally, 2 sublingually and 2 rectally.

Results
With misoprostol there was a trend to reduced blood loss ≥500 ml in 1 hour after enrolment measured in a flat plastic 'fracture bedpan', the primary outcome (6/117 vs 11/120, relative risk 0.56; 95% confidence interval 0.21 to 1.46). There was no difference in mean blood loss or haemoglobin level on day 1 after birth < 6 g/dl or blood transfusion. Side-effects were increased, namely shivering (63/116 vs 30/118; 2.14, 1.50 to 3.04) and pyrexia > 38.5°C (11/114 vs 2/118; 5.69, 1.29 to 25). In the misoprostol group 3 women underwent hysterectomy of whom 1 died, and there were 2 further maternal deaths.

Conclusions
Because of a lower than expected incidence of the primary outcome in the placebo group, the study was underpowered. We could not confirm the dramatic effect of misoprostol reported in several unblinded studies, but the results do not exclude a clinically important effect. Larger studies are needed to assess substantive outcomes and risks before misoprostol enters routine use.
Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors
Authors: Olsen Catherine L , Hsu Pin-Pin , Glienke Jens , Rubanyi Gabor M , Brooks Alan R 
Published: August 2004

Abstract
Background
The Hedgehog (Hh) signaling pathway regulates a variety of developmental processes, including vasculogenesis, and can also induce the expression of pro-angiogenic factors in fibroblasts postnatally. Misregulation of the Hh pathway has been implicated in a variety of different types of cancer, including pancreatic and small-cell lung cancer. Recently a putative antagonist of the pathway, Hedgehog-interacting protein (HIP), was identified as a Hh binding protein that is also a target of Hh signaling. We sought to clarify possible roles for HIP in angiogenesis and cancer.

Methods
Inhibition of Hh signaling by HIP was assayed by measuring the induction of Ptc-1 mRNA in TM3 cells treated with conditioned medium containing Sonic hedgehog (Shh). Angiogenesis was assayed in vitro by EC tube formation on Matrigel. Expression of HIP mRNA was assayed in cells and tissues by Q-RT-PCR and Western blot. HIP expression in human tumors or mouse xenograft tumors compared to normal tissues was assayed by Q-RT-PCR or hybridization of RNA probes to a cancer profiling array.

Results
We show that Hedgehog-interacting protein (HIP) is abundantly expressed in vascular endothelial cells (EC) but at low or undetectable levels in other cell types. Expression of HIP in mouse epithelial cells attenuated their response to Shh, demonstrating that HIP can antagonize Hh signaling when expressed in the responding cell, and supporting the hypothesis that HIP blocks Hh signaling in EC. HIP expression was significantly reduced in tissues undergoing angiogenesis, including PC3 human prostate cancer and A549 human lung cancer xenograft tumors, as well as in EC undergoing tube formation on Matrigel. HIP expression was also decreased in several human tumors of the liver, lung, stomach, colon and rectum when compared to the corresponding normal tissue.

Conclusion
These results suggest that reduced expression of HIP, a naturally occurring Hh pathway antagonist, in tumor neo-vasculature may contribute to increased Hh signaling within the tumor and possibly promote angiogenesis.
Treatment of Retinopathy of Prematurity with topical ketorolac tromethamine: a preliminary study
Authors: Avila-Vazquez Medardo , Maffrand Roque , Sosa Mirta , Franco Maria , de Alvarez Beatriz Vaca , Cafferata Maria Luisa , Bergel Eduardo 
Published: August 2004

Abstract
Background
Retinopathy of Prematurity (ROP) is a common retinal neovascular disorder of premature infants. It is of variable severity, usually heals with mild or no sequelae, but may progress to blindness from retinal detachments or severe retinal scar formation. This is a preliminary report of the effectiveness and safety of a new and original use of topical ketorolac in preterm newborn to prevent the progression of ROP to the more severe forms of this disease.

Methods
From January 2001 to December 2002, all fifty nine preterm newborns with birthweight less than 1250 grams or gestational age less than 30 weeks of gestational age admitted to neonatal intensive care were eligible for treatment with topical ketorolac (0.25 milligrams every 8 hours in each eye). The historical comparison group included all 53 preterm newborns, with the same inclusion criteria, admitted between January 1999 and December 2000.

Results
Groups were comparable in terms of weight distribution, Apgar score at 5 minutes, incidence of sepsis, intraventricular hemorrhage and necrotizing enterocolitis. The duration of oxygen therapy was significantly longer in the control group. In the ketorolac group, among 43 children that were alive at discharge, one (2.3%) developed threshold ROP and cryotherapy was necessary. In the comparison group 35 children survived, and six child (17%) needed cryotherapy (Relative Risk 0.14, 95%CI 0.00 to 0.80, p = 0.041). Adjusting by duration of oxygen therapy did not significantly change these results. Adverse effects attributable to ketorolac were not detected.

Conclusions
This preliminary report suggests that ketorolac in the form of an ophthalmic solution can reduce the risk of developing severe ROP in very preterm newborns, without producing significant adverse side effects. These results, although promising, should be interpreted with caution because of the weakness of the study design. This is an inexpensive and simple intervention that might ameliorate the progression of a disease with devastating consequences for children and their families. We believe that next logical step would be to assess the effectiveness of this intervention in a randomized controlled trial of adequate sample size.
Field assessments in western Kenya link malaria vectors to environmentally disturbed habitats during the dry season
Authors: Carlson John C , Byrd Brian D , Omlin Francois X 
Published: August 2004

Abstract
Background
Numerous malaria epidemics have occurred in western Kenya, with increasing frequency over the past 20 years. A variety of hypotheses on the etiology of these epidemics have been put forth, with different implications for surveillance and control. We investigated the ecological and socioeconomic factors promoting highland malaria vectors in the dry season after the 2002 epidemic.

Methods
Investigations were conducted in Kisii District during the dry season. Aquatic habitats in were surveyed for presence of malaria vectors. Brick-making pits were further investigated for co-associations of larval densities with emergent vegetation, habitat age, and predator diversity. Indoor spray catches were completed in houses near aquatic habitats. Participatory rural appraisals (PRAs) were conducted with 147 community members.

Results
The most abundant habitat type containing Anopheles larvae was brick-making pits. Vegetation and habitat age were positively associated with predator diversity, and negatively associated with mosquito density. Indoor spray catches found that houses close to brick-making sites had malaria vectors, whereas those next to swamps did not. PRAs revealed that brick-making has grown rapidly in highland swamps due to a variety of socioeconomic pressures in the region.

Conclusion
Brick-making, an important economic activity, also generates dry season habitats for malaria vectors in western Kenya. Specifically, functional brick making pits contain less that 50% as many predator taxa and greater than 50% more mosquito larvae when compared with nearby abandoned brick making pits. Further evaluations of these disturbed, man-made habitats in the wet season may provide information important for malaria surveillance and control.