bluuebunny/crossref_metadata_2025_split huggingface dataset:
Species-specific differences in coumarin-induced hepatotoxicity as an example toxicogenomics-based approach to assessing risk of toxicity to humans
Authors: Uehara T , Kiyosawa N , Shimizu T , Omura K , Hirode M , Imazawa T , Mizukawa Y , Ono A , Miyagishima T , Nagao T , Urushidani T 
Published: May 2008

One expected result from toxicogenomics technology is to overcome the barrier because of species-specific differences in prediction of clinical toxicity using animals. The present study serves as a model case to test if the well-known species-specific difference in the toxicity of coumarin could be elucidated using comprehensive gene expression data from rat in-vivo, rat in-vitro, and human in-vitro systems. Coumarin 150 mg/kg produced obvious pathological changes in the liver of rats after repeated administration for 7 days or more. Moreover, 24 h after a single dose, we observed minor and transient morphological changes, suggesting that some early events leading to hepatic injury occur soon after coumarin is administered to rats. Comprehensive gene expression changes were analyzed using an Affymetrix GeneChip®approach, and differentially expressed probe sets were statistically extracted. The changes in expression of the selected probe sets were further examined in primary cultured rat hepatocytes exposed to coumarin, and differentially expressed probe sets common to the in-vivo and in-vitro datasets were selected for further study. These contained many genes related to glutathione metabolism and the oxidative stress response. To incorporate human data, human hepatocyte cultured cells were exposed to coumarin and changes in expression of the bridging gene set were examined. In total, we identified 14 up-regulated and 11 down-regulated probe sets representing rat–human bridging genes. The overall responsiveness of these genes to coumarin was much higher in rats than humans, consistent with the reported species difference in coumarin toxicity. Next, we examined changes in expression of the rat–human bridging genes in cultured rat and human hepatocytes treated with another hepatotoxicant, diclofenac sodium, for which hepatotoxicity does not differ between the species. Both rat and human hepatocytes responded to the marker genes to the same extent when the same concentrations of diclofenac sodium were exposed. We conclude that toxicogenomics-based approaches show promise for overcoming species-specific differences that create a bottleneck in analysis of the toxicity of potential therapeutic treatments.
Regulation of oxidative stress–mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice
Authors: Prasad S , Kalra N , Srivastava S , Shukla Y 
Published: May 2008

Diallyl sulfide, a sulfur-containing volatile compound present in garlic ( Allium sativum), exerts anticarcinogenic activity in various rodent tumor models. In the present study, apoptosis-inhibiting effects of diallyl sulfide against a carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethyl benz(a)anthracene (DMBA), in Swiss albino mice were observed. The animals were given either 250 μg/mouse or 500 μg/mouse of diallyl sulfide for 1 week after a single intragastric dose of 7,12-dimethyl benz(a)anthracene (50 mg/kg body weight). Results showed that diallyl sulfide supplementation effectively protects against 7,12-dimethyl benz(a)anthracene—induced oxidative stress, characterized by restored antioxidant enzyme levels (up to 64%) and lipid peroxidation (up to 25%). Flow cytometric analysis showed a reduction in apoptotic cell population in hypodiploid region in diallyl sulfide–supplemented animals. Inhibition of apoptosis was preceded by decrease in reactive oxygen species levels and restoration of mitochondrial transmembrane potential followed by decreased DNA fragmentation. In 7,12-dimethyl benz(a)anthracene–exposed animals, downregulation (~30%) of antiapoptotic Bcl-2 and upregulation (~60%) of pro-apoptotic Bax proteins were observed. These alterations were restored significantly by diallyl sulfide supplementation, indicating inhibition of apoptosis. Thus, these results show that diallyl sulfide provides protection against oxidative damage induced by 7,12-dimethyl benz(a)anthracene in mouse liver and may be an effective chemopreventive and therapeutic agent by modulating expression of cell-growth regulatory proteins.
Dasatinib crosses the blood-brain barrier and is an efficient therapy for central nervous system Philadelphia chromosome–positive leukemia
Authors: Porkka Kimmo , Koskenvesa Perttu , Lundán Tuija , Rimpiläinen Johanna , Mustjoki Satu , Smykla Richard , Wild Robert , Luo Roger , Arnan Montserrat , Brethon Benoit , Eccersley Lydia , Hjorth-Hansen Henrik , Höglund Martin , Klamova Hana , Knutsen Håvar , Parikh Suhag , Raffoux Emmanuel , Gruber Franz , Brito-Babapulle Finella , Dombret Hervé , Duarte Rafael F. , Elonen Erkki , Paquette Ron , Zwaan C. Michel , Lee Francis Y. F. 
Published: May 2008

Abstract
Although imatinib, a BCR-ABL tyrosine kinase inhibitor, is used to treat acute Philadelphia chromosome–positive (Ph+) leukemia, it does not prevent central nervous system (CNS) relapses resulting from poor drug penetration through the blood-brain barrier. Imatinib and dasa-tinib (a dual-specific SRC/BCR-ABL kinase inhibitor) were compared in a preclinical mouse model of intracranial Ph+ leukemia. Clinical dasatinib treatment in patients with CNS Ph+ leukemia was assessed. In preclinical studies, dasatinib increased survival, whereas imatinib failed to inhibit intracranial tumor growth. Stabilization and regression of CNS disease were achieved with continued dasa-tinib administration. The drug also demonstrated substantial activity in 11 adult and pediatric patients with CNS Ph+ leukemia. Eleven evaluable patients had clinically significant, long-lasting responses, which were complete in 7 patients. In 3 additional patients, isolated CNS relapse occurred during dasatinib therapy; and in 2 of them, it was caused by expansion of a BCR-ABL–mutated dasatinib-resistant clone, implying selection pressure exerted by the compound in the CNS. Dasatinib has promising therapeutic potential in managing intracranial leukemic disease and substantial clinical activity in patients who experience CNS relapse while on imatinib therapy. This study is registered at ClinicalTrials.gov as CA180006 (#NCT00108719) and CA180015 (#NCT00110097).
Expression analysis of carbohydrate antigens in ductal carcinoma in situof the breast by lectin histochemistry
Authors: Korourian Soheila , Siegel Eric , Kieber-Emmons Thomas , Monzavi-Karbassi Behjatolah 
Published: May 2008

Abstract

Background
The number of breast cancer patients diagnosed with ductal carcinoma in situ (DCIS) continues to grow. Laboratory and clinical data indicate that DCIS can progress to invasive disease. Carbohydrate-mediated cell-cell adhesion and tumor-stroma interaction play crucial roles in tumorigenesis and tumor aggressive behavior. Breast carcinogenesis may reflect quantitative as well as qualitative changes in oligosaccharide expression, which may provide a useful tool for early detection of breast cancer. Because tumor-associated carbohydrate antigens (TACA) are implicated in tumor invasion and metastasis, the purpose of this study was to assess the expression of selected TACA by lectin histochemistry on DCIS specimens from the archival breast cancer tissue array bank of the University of Arkansas for Medical Sciences.

Methods
For detection of TACA expression, specimens were stained with Griffonia simplicifolia lectin-I (GS-I) and Vicia vilosa agglutinin (VVA). We studied associations of lectin reactivity with established prognostic factors, such as tumor size, tumor nuclear grade, and expression of Her-2/neu, p53 mutant and estrogen and progesterone receptors.

Results
We observed that both lectins showed significant associations with nuclear grade of DCIS. DCIS specimens with nuclear grades II and III showed significantly more intense reactivity than DCIS cases with nuclear grade I to GS-1 (Mean-score chi-square = 17.60, DF = 2; P = 0.0002) and VVA (Mean-score chi-square = 15.72, DF = 2; P = 0.0004).

Conclusion
The results suggest that the expression of VVA- and GS-I-reactive carbohydrate antigens may contribute to forming higher grade DCIS and increase the recurrence risk.
Geographical spread of gastrointestinal tract cancer incidence in the Caspian Sea region of Iran: Spatial analysis of cancer registry data
Authors: Mohebbi Mohammadreza , Mahmoodi Mahmood , Wolfe Rory , Nourijelyani Keramat , Mohammad Kazem , Zeraati Hojjat , Fotouhi Akbar 
Published: May 2008

AbstractBackgroundHigh incidence rates of gastrointestinal tract cancers have been reported in the Caspian region of Iran. This study aimed to: 1) describe the geographical spatial patterns of gastrointestinal tract cancer incidence based on cancer registry data and, 2) determine whether geographical clusters of statistical significance exist.MethodsThe Babol Cancer Registry, which covers the two major northern Iranian provinces of Mazandaran and Golestan (total population = 4,484,622) was used to identify new gastrointestinal tract cancer cases during 2001 to 2005. Age-specific cancer incidence rates were calculated for 7 gastrointestinal tract cancer sites in 26 wards of the Mazandaran and Golestan provinces. Spatial autocorrelation indices, hierarchical Bayesian Poisson models, and spatial scan statistics were used in measuring the geographic pattern and clusters.ResultsThere were non-random spatial patterns in esophageal and stomach cancers that were similar for both sexes. Clusters of high incidence were identified in esophageal, stomach, colorectal and liver cancer for both sexes, as well as a possible cluster of pancreas cancer in males.ConclusionGastrointestinal tract cancers exhibit significant spatial clustering of risk in northern Iran. Further work is needed to relate these geographical patterns to information on potential life-style and environmental factors.
Osseous metaplasia in an ulcerating tubular adenoma of the colon: a case report
Authors: White Victoria , Shaw Aidan G , Tierney Gillian M , Lund Jonathan N , Semeraro David 
Published: May 2008

Abstract

Introduction
Heterotopic bone is rarely found in the gastrointestinal tract. Here we report a rare case of metaplastic ossification within a benign ulcerating adenoma and review the literature concerning the aetiology.

Case presentation
A 63-year-old woman, who presented with a history of melaena, was found at colonoscopy to have a pedunculated ulcerating polyp. Histological examination demonstrated multiple areas of osseous metaplasia within the polyp stroma.

Conclusion
Heterotopic ossification in colonic adenomas is a particularly rare phenomenon, with the majority of cases occurring within malignant lesions. The suggested mechanisms for its aetiology still remain unclear.
Value of Fractional Uric Acid Excretion in Differential Diagnosis of Hyponatremic Patients on Diuretics
Authors: Fenske Wiebke , Störk Stefan , Koschker Ann-Cathrin , Blechschmidt Anne , Lorenz Daniela , Wortmann Sebastian , Allolio Bruno 
Published: May 2008

AbstractBackground: The syndrome of inappropriate antidiuresis (SIAD) is the most frequent cause of hyponatremia. Its diagnosis requires decreased serum osmolality, inappropriately diluted urine (e.g. &gt;100 mOsm/kg), clinical euvolemia, and a urinary sodium (Na) excretion (U-Na) more than 30 mmol/liter. However, in hyponatremic patients taking diuretics, this definition is unreliable due to the natriuretic effect of diuretics. Here, we examined the diagnostic potential of alternative laboratory measurements to diagnose SIAD, regardless of the use of diuretics.Methods: A total of 86 consecutive hyponatremic patients (serum Na &lt;130 mmol/liter) was classified based on their history, clinical evaluation, osmolality, and saline response to isotonic saline into a SIAD and a non-SIAD group. U-Na, serum urate concentration, and fractional excretion (FE) of Na, urea, and uric acid (UA) were measured in all subjects. The accuracy to diagnose SIAD was assessed using receiver operating characteristic analysis.Results: A total of 31 patients (36%) had a diagnosis of SIAD, and 55 (64%) were classified as non-SIAD. There were 57 patients (68%) who were on diuretics (15 in the SIAD group, 42 in the non-SIAD group). In the absence of diuretic therapy, SIAD was accurately diagnosed using U-Na (area under the receiver operating characteristic curve 0.96; 0.92–1.02). However, in patients on diuretics, the diagnosis was unreliable (area under the curve 0.85; 0.73–0.97). There, FE-UA performed best compared with all other markers tested (area under the curve 0.96; 0.92–1.12), resulting in a positive predictive value of 100% if a cutoff value of 12% was used.Conclusion: FE-UA allows the diagnosis of SIAD with excellent specificity. Combining the information on U-Na and FE-UA leads to a very high diagnostic accuracy in hyponatremic patients with and without diuretic treatment.
Neuroprotective effect of progesterone on acute phase changes induced by partial global cerebral ischaemia in mice
Authors: Aggarwal Raman , Medhi Bikash , Pathak Ashis , Dhawan Veena , Chakrabarti Amitava 
Published: May 2008

AbstractThe possible neuroprotective effect of progesterone, a steroid hormone, on acute phase changes in a mouse model of cerebral ischaemia induced by bilateral common carotid artery occlusion (BCAO) was studied. A total of 72 male mice were included in the study. The BCAO model was used to induce partial global cerebral ischaemia. Morphological assessment included measurement of infarct size and brain oedema. Post-ischaemic seizure susceptibility was assessed using a subconvulsive dose of pentylenetetrazole (30 mgkg−1 i.p.). Biochemical estimations included tumour necrosis factor α (TNF-α) levels and enzyme parameters such as lipid peroxidation, superoxide dismutase, catalase and glutathione peroxidase, and protein estimation. BCAO induced a significant infarct size and oedema in the saline-treated control group, along with an increase in oxidative stress, indicated by increased lipid peroxidation and decreased levels of antioxidants such as superoxide dismutase, catalase and glutathione peroxidase. Progesterone (15 mgkg−1 i.p.) administration showed a neuroprotective effect by significantly reducing the cerebral infarct size as compared with the control group. Post-ischaemic seizure susceptibility was also reduced as the number of positive responders decreased. Brain oedema subsided, but not significantly. Progesterone significantly reduced TNF-α levels compared with the ischaemia group. Progesterone improved levels of all the anti-oxidants, indicating activity against oxidative stress induced by BCAO. The results demonstrate the neuroprotective effect of progesterone against ischaemic insult, suggesting a role for the steroid as a neuroprotective agent.
Effects of Heteroatom Substitution on the Structures, Physicochemical Properties, and Redox Behavior of Nickel(II) Complexes with Pyridine-Containing Macrocyclic Ligands
Authors: Taki Masayasu , Kawashima Yoshiaki , Sakai Naoko , Hirayama Tasuku , Yamamoto Yukio 
Published: May 2008

Abstract
Nickel(II) complexes supported by 14-membered pyridine-containing macrocyclic ligands LE (E = NH, S, and O), represented as [NiII(LNH)](ClO4)2 (1a), [NiII(LS)](ClO4)2 (2a), [NiII(LS)](ClO4)(BPh4) (2b), [NiII(LO)(CH3CN)2](ClO4)2 (3a), and [NiII(LO)(CH3CN)2](ClO4)(BPh4) (3b), have been synthesized. X-ray crystal structures of complexes 1a and 2b have square-planar structures in low-spin state, whereas complex 3b exhibits an octahedral high-spin configuration where two solvent molecules occupy the axial positions of the NiN3O1 plane. The absorption spectra of 1a and 2a in coordinating solvents show interconversion of high-/low-spin states, for which the equilibrium constants and thermodynamic parameters (ΔH0 and ΔS0) have been determined. However, in the case of complex 3a in coordinating solvent, the high-spin state dominates at temperatures ranging from −40 to 60 °C. Cyclic voltammetry of the complexes 1a and 2a in CH3CN showed a reversible wave for a NiII/NiI redox couple. The redox potential for 2a (E1⁄2=−1.20 V vs. Ag/AgNO3) is more positive than that for 1a (E1⁄2=−1.48 V). In contrast to these complexes, 3a showed an irreversible redox couple with a significantly large peak separation of 460 mV. This result indicates that the coordination geometries of the nickel complex 3a drastically change between six-coordinate NiII and four-coordinate NiI states.
Mechanistic Study on the Base-Promoted Reaction of Allylphenylsilanes to Alkenylsilanols
Authors: Imazeki Shigeaki , Sugawara Hiroo , Sano Atsunori , Akiyama Takahiko 
Published: May 2008

Abstract
On treatment of allylphenylsilanes with t-BuOK and 18-crown-6 in DMSO, isomerization of the olefinic double bond and subsequent substitution of the phenyl group with a hydroxy group took place smoothly to afford alkenylsilanol derivatives in good yields. The reaction mechanism was investigated using 18O-labeled sulfoxide. We found that a (methylsulfinyl)methyl anion generated from DMSO participated in this reaction.
Playing the Identity Card: Of Grieg, Indians, and Women
Authors: McClary Susan 
Published: May 2008

Abstract
This piece was written as a keynote to a conference, Music and Identity, held in Bergen, Norway, in September 2007 to commemorate the centennial of Edvard Grieg's death. Its author, Susan McClary, both reflects on issues of identity politics then and now—including the ways in which ethnicity and gender have operated in her own career—and explores how Grieg himself theorized his fusions between the German school of composition and Norwegian folk music. It concludes with an analysis of Grieg's “Røtnams-Knut,” from his late collection Slåtter.
U-Pb single zircon grain dating of Present fluvial and Cenozoic aeolian sediments from Gabon: consequences on sediment provenance, reworking, and erosion processes on the equatorial West African margin
Authors: Seranne Michel , Bruguier Olivier , Moussavou Mathieu 
Published: May 2008

Abstract
U-Pb ages obtained from detrital zircon from terrigenous sediments are used to determine the sources. Present fluvial sand-bars of the Ogooué river yield age spectra of detrital zircons in agreement with Archean and Early Proterozoic sources found in the drainage. The large proportion of Late Proterozoic zircons cannot be derived from primary erosion of the watershed basement rocks, since there is no formation of that age in the area.
This later group of zircons is in good agreement with reworking of the aeolian Paleogene Batéké Sands, by regressive erosion in the upper reaches of the Ogooué river, as they contain a majority of Late Proterozoic age zircons. The sources of Late Proterozoic zircons in the Batéké Sand are very distant, and transported and reworked – at least in part – by aeolian processes. Our results, together with the widely distributed Paleogene sediments over continental Africa, suggests that Paleogene was a time of subdued erosion of the cratonic areas and extensive reworking, transport and deposition within continental Africa. In contrast, our results from the Ogooué river indicate active present incision of the cratonic area, erosion of the previous continental sediments, and export of the river bed-load to the continental margin. This temporal evolution of erosion-transport-deposition is correlated with the drastic climate change that occurred during the Cenozoic, leading to a more efficient mechanical erosion, and it correlates with the increase of terrigenous flux to the margin, observed during the Neogene.
A possible capture of molybdenum during early diagenesis of dysoxic sediments
Authors: Tribovillard Nicolas , Lyons Timothy W. , Riboulleau Armelle , Bout-Roumazeilles Viviane 
Published: May 2008

Abstract
Molybdenum is a trace metal commonly used as a marker of paleoredox conditions of ancient depositional settings. Pyrite is an important molybdenum (Mo) host for enriched sedimentary rocks. In this paper we study the relationship between Mo and pyrite in the Bancs Jumeaux Formation, a Jurassic succession in northern France consisting of limestone and pyrite-rich marls. This formation is relatively enriched in Mo compared to other redox-sensitive trace metals. Our approach is grounded on bulk rock chemical analysis and delineation of two contrasting types of pyrite that can be extracted from the rocks: polyframboids and nonframboidal concretionary masses. The morphological characteristics of both morphotypes were studied using scanning electronic microscopy. The polyframboids are richer in Mo than the concretions but are not markedly enriched in other trace metals. This discrepancy in geochemical composition could result from pyrite precipitation at different times during early diagenesis. Our results tend to indicate that the polyframboids would have formed very early in reducing “microniches”, within dominantly dysoxic sediment. This early pyrite precipitation occurred at shallow depth below the sediment-water interface close to the abundant Mo source in overlying oxic seawater (molybdate ions), and would have fostered Mo-capture by the polyframboids in relatively large amounts. The concretions would have formed later during early diagenesis (within the sulfidic zone) under conditions of more limited Mo availability.
Late Holocene palaeohydrology of lake Afourgagh (Middle-Atlas, Morocco) from deposit geometry and facies
Authors: Detriche Sebastien , Breheret Jean-Gabriel , Zarki Hamid , Karrat L’houcine , Macaire Jean-Jacques , Fontugne Michel 
Published: May 2008

AbstractThe geometry and facies of deposits in lake Afourgagh (Middle-Atlas, Morocco) provide evidence for successive major lake level fluctuations during the last 2,500 years. Sedimentation is mainly biogenic with the laying down of thick charophyte-rich tufas interbedded with silty layers in distal areas and palaeosols in proximal areas. These alternations point to four major deposit sequences with lowstand phases. The first two phases are dated at ca. 2426 and 1869 cal B.P. These events appear to be linked to major arid episodes on a regional scale. However, climatic impact has been modulated by human activities, particularly during recent decades.
The ‘Mur des douaniers’, an exceptionally well-preserved Early Eifelian fossil site
Authors: Crônier Catherine , van Viersen Allart 
Published: May 2008

AbstractThe ‘Mur des douaniers’ biota at the former French/Belgian border contains a rich and diversified Lower Eifelian benthic fauna, and especially trilobites. Palaeobiodiversity and sedimentological analyses have led to the interpretation of the general palaeoenvironmental/palaeoecological context. This trilobite-rich locality is an exceptionally well-preserved Early Eifelian fossil site with regard to the regional scale. Unfortunately, its growing reputation led to fossil pillage and now this palaeontological site is protected as a Nature Reserve. From now on, no complementary observation of the palaeontological data, the taphonomic analysis, the ichnological, sedimentological and geochemical record can be made to provide a better palaeoecological synthesis.