bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcranial Doppler ultrasonography-directed intravenous glycoprotein IIb/IIIa receptor antagonist therapy to control transient cerebral microemboli before and after carotid endarterectomy
Authors: van Dellen D , Tiivas C A S , Jarvi K , Marshall C , Higman D J , Imray C H E
Published: April 2008

Background

Patients with a transient focal neurological deficit, critical carotid stenosis and/or microemboli detected by transcranial Doppler ultrasonography (TCD) have a significant risk of stroke. The effect of tirofiban, a selective glycoprotein IIb/IIIa inhibitor, was assessed in patients with microembolic signals on TCD after transient ischaemic attacks or carotid endarterectomy (CEA).

Methods

Thirty-three patients with microemboli on TCD (13 symptomatic preoperative, 19 postoperative, one both) were treated with tirofiban between 2002 and 2007. All patients had carotid stenosis greater than 70 per cent. TCD monitoring was used during and after tirofiban therapy.

Results

The median (range) rate of microemboli decreased from 22 (4–260) per h before surgery and 81 (44–216) per h after surgery to 0 (0–9) per h in both groups (P < 0·001, Mann–Whitney U test). This occurred rapidly (preoperative median 30 min; postoperative median 45 min) and was well tolerated in all patients, with no serious adverse effects.

Conclusion

Cerebral microemboli were controlled by tirofiban both before and after CEA. Further study is required to compare the relative efficacy of tirofiban and dextran.
Malformation of True Bug (Heteroptera): a Phenotype Field Study on the Possible Influence of Artificial Low‐Level Radioactivity
Authors: Hesse‐Honegger Cornelia , Wallimann Peter
Published: April 2008

The results of extensive field studies on the malformation of Western European true bugs (Heteroptera) are reviewed. More than 16,000 individuals were collected over two decades, and subjected to detailed visual inspection. Various types of disturbances were found and illustrated in detail. Depending on country, region, as well as local influences, severe disturbances and high degrees of malformation were noticed, especially in the sphere of nuclear‐power installations in Switzerland (Aargau), France (La Hague), and Germany (Gundremmingen). Malformation reached values as high as 22 and 30% for morphological (MD) and total disturbance (TD), respectively. This is far above the values expected for natural populations (ca. 1%) or those determined for true bugs living in biotopes considered as relatively ‘intact’ (1–3%). A detailed chi‐square test of the malformation data obtained for 650 true bugs from 13 collection sites near the nuclear‐reprocessing plant La Hague showed a highly significant correlation (p=0.003) between malformation and wind exposure/local topography. Similar observations were made for other study sites. Currently, our data are best rationalized by assuming a direct influence between the release of anthropogenic radionuclides such as tritium (3H), carbon‐14 (14C), or iodine‐131 (131I), constantly emitted by nuclear‐power and nuclear‐reprocessing plants, as well as by Chernobyl and bomb‐testing fallout, which is rich in caesium‐137 (137Cs) and other long‐lived noxious isotopes that have entered the food chain. The present work supports the growing evidence that low‐level radiation, especially in the form of randomly scattered ‘hot’ α‐ and β‐particles, mainly transported via aerosols, puts a heavy burden on the biosphere in general, and on true bugs in particular. These insects could, thus, serve as sensitive ‘bio‐indicators’ for future studies.
Novel Single‐Crystal‐to‐Single‐Crystal Anion Exchange and Self‐Assembly of Luminescent d10 Metal (CdII, ZnII, and CuI) Complexes Containing C3‐Symmetrical Ligands
Authors: Tzeng Biing‐Chiau , Chiu Tse‐Hao , Chen Bo‐So , Lee Gene‐Hsiang
Published: April 2008

Ligands L1 and L2′ (L1=N,N′,N′′‐tris(4‐pyridyl)trimesic amide, L2′=N,N′,N′′‐tris(3‐pyridinyl)‐1,3,5‐benzenetricarboxamide) belonging to an interesting family of tripyridyltriamides with C3‐symmetry have been utilized to construct 3D porous or hydrogen‐bonded frameworks. Through a novel single‐crystal‐to‐single‐crystal anion‐exchange process, [Cd(L1)2(ClO4)2]n (1 c) can be obtained from [Cd(L1)2Cl2]n (1 b) in the presence of ClO4− anions. This anion‐exchange process is highly selective and only the substitution of Cl− by ClO4− or PF6− could be realized; Cl− was found not to be substituted by BPh4−. This demonstrates that the exchange process depends on the size of the anions in relation to the size of the cavities in the host material (ca. 7.5 Å). In addition, the anion‐exchange properties of 1 b have also been investigated by means of powder X‐ray diffraction (PXRD), elemental analysis (EA), and infrared absorption spectroscopy (IR). Structurally, [Zn(L1)(NO3)2]n (2) consists of a 2D coordination network with five‐coordinate ZnII ions. Surprisingly, different trigonal‐bipyramidal ZnII ions propagate to form distinct respective sheet structures, A and B, which are packed in an A‐B‐A‐B manner in the crystal lattice, and these are hydrogen‐bonded to give a 3D extended framework. The molecular structure of [CuI(L2′)]n (3) shows that the CuI ion adopts a distorted tetrahedral geometry, and 3 also forms a 2D coordination network. Significantly, this 2D coordination network is further assembled into a remarkable 3D homochiral framework through triple hydrogen bonding and π⋅⋅⋅π interactions. All of these 3D coordination polymers and/or hydrogen‐bonded frameworks are luminescent in the solid state, and their solid‐state luminescent properties have been investigated at room temperature and/or at 77 K.
New Mono‐ and Dimeric Members of the Secalonic Acid Family: Blennolides A–G Isolated from the Fungus Blennoria sp.
Authors: Zhang Wen , Krohn Karsten , Zia‐Ullah  , Flörke Ulrich , Pescitelli Gennaro , Di Bari Lorenzo , Antus Sándor , Kurtán Tibor , Rheinheimer Joachim , Draeger Siegfried , Schulz Barbara
Published: April 2008

Blennolides A–G (2–8), seven unusual chromanones, were isolated together with secalonic acid B (1) from Blennoria sp., an endophytic fungus from Carpobrotus edulis. This is the first reported isolation of the blennolides 2 and 3 (hemisecalonic acids B and E), the existence of which as the monomeric units of the dimeric secalonic acids had long been postulated. A compound of the proposed structure 4 (β‐diversonolic ester) will need to be revised, as its reported data do not fit those of the established structure of blennolide C (4). Other monomers, the blennolides D–F (5–7) seem to be derived from blennolides A (2) and B (3) by rearrangement of the hydroaromatic ring. The heterodimer 8, composed of the monomeric blennolide A (2) and the rearranged 11‐dehydroxy derivative of blennolide E (6), extends the ergochrome family with an ergoxanthin type of skeleton. The structures of the new compounds were elucidated by detailed spectroscopic analysis and further confirmed by an X‐ray diffraction study of a single crystal of 2. The absolute configurations were determined by TDDFT calculations of CD spectra, including the solid‐state CD/TDDFT approach. Preliminary studies showed strong antifungal and antibacterial activities of these compounds against Microbotryum violaceum and Bacillus megaterium, respectively. They were also active against the alga Chlorella fusca and the bacterium Escherichia coli.
Similar Biological Activities of Two Isostructural Ruthenium and Osmium Complexes
Authors: Maksimoska Jasna , Williams Douglas S. , Atilla‐Gokcumen G. Ekin , Smalley Keiran S. M. , Carroll Patrick J. , Webster Richard D. , Filippakopoulos Panagis , Knapp Stefan , Herlyn Meenhard , Meggers Eric
Published: April 2008

In this study, we probe and verify the concept of designing unreactive bioactive metal complexes, in which the metal possesses a purely structural function, by investigating the consequences of replacing ruthenium in a bioactive half‐sandwich kinase inhibitor scaffold by its heavier congener osmium. The two isostructural complexes are compared with respect to their anticancer properties in 1205 Lu melanoma cells, activation of the Wnt signaling pathway, IC50 values against the protein kinases GSK‐3β and Pim‐1, and binding modes to the protein kinase Pim‐1 by protein crystallography. It was found that the two congeners display almost indistinguishable biological activities, which can be explained by their nearly identical three‐dimensional structures and their identical mode of action as protein kinase inhibitors. This is a unique example in which the replacement of a metal in an anticancer scaffold by its heavier homologue does not alter its biological activity.
Hydroxycruciforms: Amine‐Responsive Fluorophores
Authors: McGrier Psaras L. , Solntsev Kyril M. , Miao Shaobin , Tolbert Laren M. , Miranda Oscar R. , Rotello Vincent M. , Bunz Uwe H. F.
Published: April 2008

The synthesis of three hydroxy‐substituted cruciforms (XF, 1,4‐bis(4′‐hydroxystyryl)‐2,5‐bis(4′′‐methoxyphenylethynyl)benzene, 1,4‐bis(4′‐methoxystyryl)‐2,5‐bis(4′′‐hydroxyphenylethynyl)benzene, and 1,4‐bis(4′‐hydroxystyryl)‐2,5‐bis(4′′‐hydroxyphenylethynyl)benzene) starts with a Horner reaction followed by a Sonogashira coupling and subsequent deprotection. The three herein described XFs contain either two or four free phenolic hydroxyl groups. All three XFs were subjected to photometric UV/Vis titrations in a methanol/water mixture. The respective pKa values were obtained by data deconvolution. As the three XFs display a significant change in emission color upon photoinduced deprotonation, the XFs were taken up in different solvents and exposed to twelve amines. The amine‐dependent change in emissivity of the tetrahydroxy XF is sufficiently distinct in the eight solvents that all of the inspected amines are discerned by a linear discriminant analysis. The tetrahydroxy XF in different solvents forms a sensor array, the response of which is based on the excited‐state proton transfer (ESPT) to amines and mediated by the choice of the battery of solvents that are utilized.
Glycine receptor‐mediated synaptic transmission regulates the maturation of ganglion cell synaptic connectivity
Authors: Xu Hong‐Ping , Tian Ning
Published: April 2008

It is well documented that neuronal activity is required for the developmental segregation of retinal ganglion cell (RGC) synaptic connectivity with ON and OFF bipolar cells in mammalian retina. Our recent study showed that light deprivation preferentially blocked the developmental RGC dendritic redistribution from the center to sublamina a of the inner plexiform layer (IPL). To determine whether OFF signals in visual stimulation are required for OFF RGC dendritic development, the light‐evoked responses and dendritic stratification patterns of RGCs in Spastic mutant mice, in which the OFF signal transmission in the rod pathway is largely blocked due to a reduction of glycine receptor (GlyR) expression, were quantitatively studied at different ages and rearing conditions. The dendritic distribution in the IPL of these mice was indistinguishable from wildtype controls at the age of postnatal day (P)12. However, the adult Spastic mutants had altered RGC light‐evoked synaptic inputs from ON and OFF pathways, which could not be mimicked by pharmacologically blocking of glycinergic synaptic transmission on age‐matched wildtype animals. Spastic mutation also blocked the developmental redistribution of RGC dendrites from the center to sublamina a of the IPL, which mimicked the effects induced by light deprivation on wildtype animals. Moreover, light deprivation of the Spastic mutants had no additional impact on the RGC dendritic distribution and light response patterns. We interpret these results as that visual stimulation regulates the maturation of RGC synaptic activity and connectivity primarily through GlyR‐mediated synaptic transmission. J. Comp. Neurol. 509:53–71, 2008. © 2008 Wiley‐Liss, Inc.
The 4–1BB ligand and 4–1BB expressed on osteoclast precursors enhance RANKL‐induced osteoclastogenesis via bi‐directional signaling
Authors: Yang Jihyun , Park Ok Jin , Lee Yeon Ju , Jung Hong‐Moon , Woo Kyung Mi , Choi Youngnim
Published: April 2008

The 4–1BB is a costimulatory molecule similar to the receptor activator of NF‐κB ligand (RANKL), both of which are key factors for the differentiation of osteoclasts and are expressed mainly by activated T cells. The 4–1BB shares common signaling pathways with RANK, suggesting a potential role in osteoclastogenesis. In this study, the role of 4–1BB and 4–1BB ligand (4–1BBL) in osteoclastogenesis was investigated using 4–1BB–/– and 4–1BB+/+ mice. Osteoclast precursors normally express 4–1BB and 4–1BBL after exposure to RANKL, which was confirmed by semi‐quantitative RT‐PCR and flow cytometry. The 4–1BB–/– mice had a slightly increased bone mass accompanied by a reduced osteoclastogenic ability of 4–1BB–/– bone marrow‐derived macrophages (BMM) ex vivo. In addition, 4–1BB–/– BMM demonstrated hypophosphorylation of JNK and p38 and decreased induction of c‐Fos in response to RANKL stimulation. Retroviral transduction of wild‐type as well as partial‐length 4–1BB, which lacks TNF receptor‐associated factor 2‐binding sites for signaling, restored the osteoclastogenic ability of 4–1BB–/– BMM. Furthermore, both recombinant 4–1BB and 4–1BBL enhanced RANKL‐induced osteoclastogenesis by 4–1BB+/+ BMM and the induction of c‐Fos and NFATc1.Together, these results indicate that 4–1BBL and 4–1BB expressed on osteoclast precursors enhance RANKL‐induced osteoclastogenesis via bi–directional signaling, findings that may delineate the complex nature of the 4–1BBL and 4–1BB interaction.

Supporting Information for this article is available at www.wiley‐vch.de/contents/jc_2040/2008/37650_s.pdf
Suppression of viral replication with highly active antiretroviral therapy has no impact on the functional profile of HIV‐specific CD8+ T cells
Authors: López Mariola , Soriano Vincent , Rallón Norma , Cascajero Almudena , González‐Lahoz Juan , Benito José M.
Published: April 2008

A better control of viral replication in long‐term non‐progressors has been associated with polyfunctional CD8+ T cell responses. However, low levels of HIV replication could be the cause rather than the consequence of enhanced immune responses in long‐term non‐progressors. The functional profile and the expansion ability of HIV‐Gag‐ and HIV‐Nef‐specific CD8 responses were analysed measuring the production of MIP‐1β, IL‐2, TNF‐α and expression of CD107, using polychromatic flow cytometry, in 36 HIV‐infected patients at baseline and after 12 months of highly active antiretroviral therapy (HAART) and complete viral suppression. Most patients presented detectable Gag and Nef responses both at baseline and after 1 year of HAART, with a significant decline after achieving viral suppression. At baseline, the majority of CD8+ response was due to cells producing only MIP‐1β or simultaneously MIP‐1β and CD107. The functional profile did not significantly change after achieving complete viral suppression with HAART. Therefore, control of HIV‐1 replication after 1 year of HAART had no significant impact on the quality of HIV‐1‐specific CD8 response, but the effects of treatment in long‐term, or of early HAART are not known. Thus, it is still uncertain whether multifunctional CD8 responses are the cause or consequence of low plasma viremia.
Development of a capillary electrophoresis‐mass spectrometry method using polymer capillaries for metabolomic analysis of yeast
Authors: Tanaka Yoshihide , Higashi Tetsuji , Rakwal Randeep , Wakida Shin‐ichi , Iwahashi Hitoshi
Published: April 2008

Metabolomics is an emerging field in analytical biochemistry, and the development of such a method for comprehensive and quantitative analysis of organic acids, carbohydrates, and nucleotides is a necessity in the era of functional genomics. When a concentrated yeast extract was analyzed by CE‐MS using a successive multiple ionic‐polymer layer (SMIL)‐coated capillary, the adsorption of the contaminants on the capillary wall caused severe problems such as no elution, band‐broadening, and asymmetric peaks. Therefore, an analytical method for the analysis of anionic metabolites in yeast was developed by pressure‐assisted CE using an inert polymer capillary made from poly(ether etherketone) (PEEK) and PTFE. We preferred to use the PEEK over the PTFE capillary in CE‐MS due to the easy‐to‐use PEEK capillary and its high durability. The separation of anionic metabolites was successfully achieved with ammonium hydrogencarbonate/formate buffer (pH 6.0) as the electrolyte solution. The use of 2‐propanol washing after every electrophoresis run not only eliminated wall‐adsorption phenomena, but allowed for good repeatability to be obtained for migration times in the metabolomic analysis.
Application of capillary isotachophoresis‐based multidimensional separations coupled with electrospray ionization‐tandem mass spectrometry for characterization of mouse brain mitochondrial proteome
Authors: Fang Xueping , Wang Weijie , Yang Li , Chandrasekaran Krish , Kristian Tibor , Balgley Brian M. , Lee Cheng S.
Published: April 2008

By employing a capillary ITP (CITP)/CZE‐based proteomic technology, a total of 1795 distinct mouse Swiss‐Prot protein entries (or 1705 nonredundant proteins) are identified from synaptic mitochondria isolated from mouse brain. The ultrahigh resolving power of CITP/CZE is evidenced by the large number of distinct peptide identifications measured from each CITP fraction together with the low peptide fraction overlapping among identified peptides. The degree of peptide overlapping among CITP fractions is even lower than that achieved using combined CIEF/nano‐RP LC separations for the analysis of the same mitochondrial sample. When evaluating the protein sequence coverage by the number of distinct peptides mapping to each mitochondrial protein identification, CITP/CZE similarly achieves superior performance with 1041 proteins (58%) having 3 or more distinct peptides, 233 (13%) having 2 distinct peptides, and 521 (29%) having a single distinct peptide. The reproducibility of protein identifications is found to be around 86% by comparing proteins identified from repeated runs of the same mitochondrial sample. The analysis of the mouse mitochondrial proteome by two CITP/CZE runs results in the detection of 2095 distinct mouse Swiss‐Prot protein entries (or 1992 nonredundant proteins), corresponding to 59% coverage of the updated Maestro mitochondrial reference set. The collective analysis from combined CITP/CZE and CIEF‐based proteomic studies yields the identification of 2191 distinct mitochondrial protein entries (or 2082 nonredundant proteins), corresponding to 76% coverage of the MitoP2‐database reference set.
Analysis of intact erythropoietin and novel erythropoiesis‐stimulating protein by capillary electrophoresis‐electrospray‐ion trap mass spectrometry
Authors: Giménez Estela , Benavente Fernando , Barbosa José , Sanz‐Nebot Victoria
Published: April 2008

Recombinant human erythropoietin (rHuEPO) and novel erythropoiesis‐stimulating protein (NESP) were analyzed by CE‐ESI‐MS using an IT as analyzer. The IT parameters were optimized by direct infusion of solutions of different intact proteins (myoglobin, transferrin, α1‐acid glycoprotein and fetuin) with different degrees of glycosylation (from 0 to 35% w/w). Two physically adsorbed capillary coatings from UltraTol™ Pre‐Coats (low normal (LN) and high reverse (HR)) were evaluated for the separation of rHuEPO and NESP glycoforms by CE‐ESI‐IT‐MS. The results obtained with the neutral LN coating suggest that an IT mass spectrometer enables identification of the main glycoforms of a complex glycoprotein such as rHuEPO. Although LN provided acceptable glycoform resolution for rHuEPO, the separation obtained for NESP was less significant due to the higher microheterogeneity of this glycoprotein. Reproducibility studies confirmed the lack of stability and bleeding of the LN coating, which caused problems with MS detection, such as a dramatic loss of sensitivity and the presence of peaks in the mass spectra corresponding to molecular ions in the coating. In contrast, the cationic HR coating gave faster but poorer glycoform separations due to the presence of an anodal EOF. However, the positive charge of the coating provided enhanced hydrolytic stability, making it more suitable than the LN coating for the on‐line MS coupling.
Identification of toxic oligopeptides in Amanita fungi employing capillary electrophoresis‐electrospray ionization‐mass spectrometry with positive and negative ion detection
Authors: Rittgen Jan , Pütz Michael , Pyell Ute
Published: April 2008

The identification of toxic oligopeptides employing CE‐ESI‐MS is presented. The analytes studied ama‐ and phallotoxins are of significant forensic interest because over 90% of the lethal cases of fungus poisoning in man are caused by species of Amanita which contain these toxins. A CE method was developed to separate the toxins α‐, β‐ and γ‐amanitin, phalloidin and phallacidin. Their fragmentation patterns in MSn experiments were investigated in the positive and in the negative ion mode, also the influence of the sheath liquid mixture of the used interface on the S/N. Method validation included the determination of the LOD and the repeatability of the migration time and peak area for both detection modes. With the optimized method LODs of 13–79 ng/mL (17–87 nmol/L) were reached. The CE‐MS procedure was successfully applied to the identification of ama‐ and phallotoxins in extracts of air‐dried mushroom samples.
The loudness dependence of the auditory evoked potential (LDAEP) as anin vivobiomarker of central serotonergic function in humans: rationale, evaluation and review of findings
Authors: O'Neill Barry V. , Croft Rodney J. , Nathan Pradeep J.
Published: April 2008

Objectives

The loudness dependence of the auditory evoked potential (LDAEP) has been proposed as a valid means of non‐invasively assessingin vivocentral serotonin (5‐hydroxytryptamine, 5‐HT) function in humans. The specificity and sensitivity of the LDAEP to changes in 5‐HT neurotransmission have recently been explored directly in a number of pharmacological and genetic studies. Subsequently, this review was undertaken in an attempt to critically evaluate the potential role of the LDAEP as a marker of the central 5‐HT function.

Design

Findings from clinical, experimental animal and human studies examining the relationship between the LDAEP and the 5‐HT system as well as other neurochemical systems including dopaminergic, glutamatergic and the cholinergic systems were reviewed.

Results

The majority of evidence for an association between the LDAEP and 5‐HT has come from animal studies. Indirect studies in clinical disorders of presumed serotonergic dysfunction have been circumstantial and inconsistent with more recent investigations utilising direct genetic association studies also providing conflicting reports. Pharmacological studies in humans provide overwhelming evidence that the LDAEP is insensitive to acute changes in 5‐HT function, with additional evidence outlining sensitivity to other neurotransmitter systems including the glutamatergic system.

Conclusions

The available evidence suggests that the LDAEP lacks sensitivity and specificity to acute changes in serotonergic neurotransmission. Overall the findings do not provide strong support for its utility as a marker of central 5‐HT function. However the LDAEP shows more promise as a potential predictor of antidepressant treatment response and this predictive ability may provide the basis for future research involving the LDAEP. Copyright © 2008 John Wiley & Sons, Ltd.
Executive function deficits in short‐term abstinent cannabis users
Authors: McHale Sue , Hunt Nigel
Published: April 2008

Objectives

Few cognitive tasks are adequately sensitive to show the small decrements in performance in abstinent chronic cannabis users. In this series of three experiments we set out to demonstrate a variety of tasks that are sufficiently sensitive to show differences in visual memory, verbal memory, everyday memory and executive function between controls and cannabis users.

Methods

A series of three studies explored cognitive function deficits in cannabis users (phonemic verbal fluency, visual recognition and immediate and delayed recall, and prospective memory) in short‐term abstinent cannabis users. Participants were selected using snowball sampling, with cannabis users being compared to a standard control group and a tobacco‐use control group.

Results

The cannabis users, compared to both control groups, had deficits on verbal fluency, visual recognition, delayed visual recall, and short‐ and long‐interval prospective memory. There were no differences for immediate visual recall.

Conclusions

These findings suggest that cannabis use leads to impaired executive function. Further research needs to explore the longer term impact of cannabis use. Copyright © 2008 John Wiley & Sons, Ltd.
The use of effect sizes to characterize the nature of cognitive change in psychopharmacological studies: an example with scopolamine
Authors: Fredrickson Amy , Snyder Peter J. , Cromer Jennifer , Thomas Elizabeth , Lewis Matthew , Maruff Paul
Published: April 2008

Drug induced cognitive change is generally investigated using small sample sizes. In terms of null hypothesis significance testing (NHST) this can render a meaningful change non‐significant, as a result of insufficient power in the statistical model. NHST leads to ‘all or none’ thinking, where a non‐significant result is interpreted as an absence of change. An effect size calculation indicates the magnitude of change which has occurred post‐intervention, and therefore whether a significant result is meaningful. We used a scopolamine challenge to demonstrate the usefulness of effect sizes. The aim of the study was to determine how effect sizes could describe the cognitive changes that occur following administration of subcutaneous scopolamine (s.c. scopolamine). Twenty four healthy young males (M = 32.6, sd = 4.5 years) were administered placebo and 0.2 mg, 0.4 mg & 0.6 mg of s.c. scopolamine using a 4‐way crossover design. Memory, learning, psychomotor function, attention and executive function were assessed. Scopolamine significantly impaired performance on all tasks in a dose and time related manner. These results demonstrate the functionality of change scores to draw comparisons between different times and doses. This methodology overcomes the limitations of comparisons between studies using different tasks, doses and time at which cognitive functions are measured. Copyright © 2008 John Wiley & Sons, Ltd.
The aberrant methylation of TSP1 suppresses TGF‐β1 activation in colorectal cancer
Authors: Rojas Andres , Meherem Shereen , Kim Young‐Ho , Washington Mary Kay , Willis Joseph E. , Markowitz Sanford D. , Grady William M.
Published: April 2008

Colorectal cancer arises from the progressive accumulation of mutations and epigenetic alterations in colon epithelial cells. Such alterations often deregulate signaling pathways that affect the formation of colon cancer, such as the Wnt, RAS‐MAPK and TGF‐β pathways. The tumor promoting effects of mutations in genes, such as APC, have been demonstrated in cancer cell lines and in mouse models of intestinal cancer; however, the biological effects of most epigenetic events identified in colorectal cancer remain unknown. Consequently, we assessed whether the aberrant methylation of TSP1, the gene for thrombospondin 1, a regulator of TGF‐β ligand activation, is an epigenetic mechanism for inhibiting the TGF‐β signaling pathway. We found methylated TSP1 occurs in colon cancer cell lines (33%), colon adenomas (14%) and colon adenocarcinomas (21%). In primary colorectal cancers, loss of TSP1 expression correlated with impaired TGF‐β signaling as indicated by decreased Smad2 phosphorylation and nuclear localization. Furthermore, methylation‐induced silencing of TSP1 expression reduced the concentration of secreted active TGF‐β1 and attenuated TGF‐β signaling. Reversal of TSP1 methylation resulted in increased TSP1 mediated activation of the latent LAP:TGF‐β complex and subsequent TGF‐β receptor activation. Our results demonstrate that the aberrant methylation of TSP1 has biological consequences and provide evidence that the aberrant methylation of TSP1 is a novel epigenetic mechanism for suppressing TGF‐β signaling in colorectal cancer. © 2008 Wiley‐Liss, Inc.
p21 is required for atRA‐mediated growth inhibition of MEPM cells, which involves RAR
Authors: Yu Zengli , Li Wenjie , Lu Quanjun , Wang Ling , Zhang Xiaofeng , Han Ping , Chen Pingping , Pei Yingxin
Published: April 2008

All‐trans retinoic acid (atRA), a metabolite of vitamin A, is essential for embryonic development. Thus the spatial and temporal dispersal of RA must be tightly controlled. Previous studies show that excessive atRA led to growth inhibition and p21 accumulation in mouse embryonic palatal mesenchymal (MEPM) cells. We reported here the identification of p21 as a required mediator during atRA‐induced growth inhibition. atRA caused a G1 arrest in the cell cycle with an increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S phase. In addition to a marked effect on cell cycling, atRA also triggered DNA fragmentation, reflected by an increase of the fraction of cells in the sub‐G1population. Western blot analysis revealed that atRA treatment led to an increase in p21 level and a decrease in cyclin D1 protein and Rb phosphorylation. Using luciferase assay with reporter gene regulated by p21 promoter, we showed that atRA increased the reporter activity in a dose‐dependent manner; and p21 siRNA blocked the growth inhibition by atRA, suggesting that p21 is required for atRA‐mediated growth inhibition. Moreover, the induction of p21 by atRA was partially attenuated when RAR was silenced with specific siRNA. atRA stimulated RARE‐driven reporter gene activity dose‐dependently. Using chromatin immunoprecipitation, we demonstrated that RAR protein could bind to the p21 promoter. Taken together, our results indicate p21 is responsible for atRA‐induced growth inhibition of MEPM cells and RAR plays a role during this process. J. Cell. Biochem. 104: 2185–2192, 2008. © 2008 Wiley‐Liss, Inc.
Feminist identity as a predictor of eating disorder diagnostic status
Authors: Green Melinda A. , Scott Norman A. , Riopel Cori M. , Skaggs Anna K.
Published: April 2008

Passive Acceptance (PA) and Active Commitment (AC) subscales of the Feminist Identity Development Scale (FIDS) were examined as predictors of eating disorder diagnostic status as assessed by the Questionnaire for Eating Disorder Diagnoses (Q‐EDD). Results of a hierarchical regression analysis revealed PA and AC scores were not statistically significant predictors of ED diagnostic status after controlling for diagnostic subtype. Results of a multiple regression analysis revealed FIDS as a statistically significant predictor of ED diagnostic status when failing to control for ED diagnostic subtype. Discrepancies suggest ED diagnostic subtype may serve as a moderator variable in the relationship between ED diagnostic status and FIDS. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:777–788, 2008.
Predicting individual differences in autonomy‐connectedness: the role of body awareness, alexithymia, and assertiveness
Authors: Bekker Marrie H. J. , Croon Marcel A. , van Balkom Esther G. A. , Vermee Jennifer B. G.
Published: April 2008

Autonomy‐connectedness is the capacity for being on one's own as well as for satisfactorily engaging in interpersonal relationships. Associations have been shown between autonomy‐connectedness components (self‐awareness, sensitivity to others, and the capacity for managing new situations) and various indices of psychopathology. Both in a theoretical sense as well as for enhancing treatment and prevention, it is relevant to identify which factors most powerfully predict individual differences in autonomy‐connectedness: body awareness, alexithymia, or assertiveness. The present study examined this question in a clinical sample of women who were diagnosed as having autonomy problems (N=52) and in a female nonclinical community sample (N=59). In line with expectations, assertiveness was a strong predictor of (all three components of) autonomy‐connectedness, as was emotionalizing, one of the alexithymia‐components, but the latter in an opposite direction than we had expected: the higher an individual's ability to emotionalize was, the less self‐aware and capable to manage new situations that person was, and the more sensitive to others. Cognitive alexithymia contributed to self‐awareness as well as to the capacity for managing new situations, and one of the components of body awareness appeared to predict capacity for managing new situations. Our results indicate that assertiveness training and the enhancement of emotion regulation are important elements of autonomy‐connectedness targeted interventions. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:747–765, 2008.
Netrin‐1 can affect morphogenesis and differentiation of the mouse mammary gland
Authors: Strizzi Luigi , Mancino Mario , Bianco Caterina , Raafat Ahmed , Gonzales Monica , Booth Brian W. , Watanabe Kazuhide , Nagaoka Tadahiro , Mack David L. , Howard Beatrice , Callahan Robert , Smith Gilbert H. , Salomon David S.
Published: April 2008

Netrin‐1 has been shown to regulate the function of the EGF‐like protein Cripto‐1 (Cr‐1) and affect mammary gland development. Since Cr‐1 is a target gene of Nanog and Oct4, we investigated the relationship between Netrin‐1 and Cr‐1, Nanog and Oct4 during different stages of development in the mouse mammary gland. Results from histological analysis show that exogenous Netrin‐1 was able to induce formation of alveolar‐like structures within the mammary gland terminal end buds of virgin transgenic Cripto‐1 mice and enhance mammary gland alveologenesis in early pregnant FVB/N mice. Results from immunostaining and Western blot analysis show that Netrin‐1, Nanog and Oct4 are expressed in the mouse embryonic mammary anlage epithelium while Cripto‐1 is predominantly expressed outside this structure in the surrounding mesenchyme. We find that in lactating mammary glands of postnatal FVB/N mice, Netrin‐1 expression is highest while Cripto‐1 and Nanog levels are lowest indicating that Netrin‐1 may perform a role in the mammary gland during lactation. HC‐11 mouse mammary epithelial cells stimulated with lactogenic hormones and exogenous soluble Netrin‐1 showed increased beta‐casein expression as compared to control thus supporting the potential role for Netrin‐1 during functional differentiation of mouse mammary epithelial cells. Finally, mouse ES cells treated with exogenous soluble Netrin‐1 showed reduced levels of Nanog and Cripto‐1 and higher levels of beta‐III tubulin during differentiation. These results suggest that Netrin‐1 may facilitate functional differentiation of mammary epithelial cells and possibly affect the expression of Nanog and/or Cripto‐1 in multipotent cells that may reside in the mammary gland. J. Cell. Physiol. 216: 824–834, 2008, © 2008 Wiley‐Liss, Inc.
Immunophenotyping of lymphocyte subsets in the third eyelid tissue in dogs (Canis familiaris): Morphological, microvascular, and secretory aspects of this ocular adnexa
Authors: Alexandre‐Pires G. , Algueró M.C. , Mendes‐Jorge L. , Trindade H. , Correia M. , Esperança Pina J.A.
Published: April 2008

The third eyelid is an important adnexa of the eye. The objective of this study was to evaluate (i) morphological aspects (ii) vascularization, and (iii) the immunophenotype of lymphocyte subsets in the third eyelid of dogs. Flow cytometric analysis revealed the presence of three patterns concerning the immunophenotype of the third eyelid tissue. Dogs without ocular insult or deficient tear production might belong to one of the following immunophenotype patterns: I ‐ the number of T‐cells that expressed CD3+ CD8+ was higher than the number of cells that expressed CD3+CD4+. II ‐ the number of cells CD3+C4+ was higher than the number of cells CD3+CD8+ and in this case a higher number of cells that expressed CD19 were identified. III ‐ Proximity of values of the cells that expressed CD3+CD4+ and CD3+CD8+. These data might suggest that the number of lymphocyte T cells alone should not be considered a direct indicator of the presence of an immune‐based inflammation. Besides, a particular population of T‐cells does not indicate a particular inflammatory state. The morphological study of the third eyelid revealed a rather uncommon angioarchitecture. The artery that irrigates the eyelid crosses almost the entire length of this structure to achieve its free border, and only then, ramificates deeply towards an inner segmental level. This spatial microvascular arrangement probably results from an adaptation to the fact that the third eyelid, in the medial cantus of the eye, is inwardly compressed into a tiny space. Efficient vascularization is achieved by allowing the first ramifications of the third eyelid artery to run straight to the top. Accini secretor cells of the third eyelid show a mucin content while tubuloacinar cells are mainly serous. Microsc. Res. Tech., 2008. © 2008 Wiley‐Liss, Inc.
Detection of choline signal in human breast lesions with chemical‐shift imaging
Authors: Baek Hyeon‐Man , Chen Jeon‐Hor , Yu Hon J. , Mehta Rita , Nalcioglu Orhan , Su Min‐Ying
Published: April 2008

Purpose

To investigate the application of MR spectroscopy using chemical‐shift imaging (CSI) for characterizing human breast lesions at 1.5T, and to evaluate the diagnostic performance using ROC (receiver operating characteristics) analysis.

Materials and Methods

Thirty‐six patients (35–73 years old, mean 52), with 27 malignant and 9 benign lesions, underwent anatomical imaging, dynamic contrast‐enhanced MR imaging, and CSI. The ROC analysis was performed and the cutoff point yielding the highest accuracy was found to be a choline (Cho) signal‐to‐noise ratio (SNR) >3.2.

Results

The mean Cho SNR was 2.8 ± 0.8 (range, 1.8–4.3) for the benign group and 5.9 ± 3.4 (2.1–17.5) for the malignant group (P = 0.01). Based on the criterion of Cho SNR >3.2 as malignant, CSI correctly diagnosed 22 of 27 malignant lesions and 7 of 9 benign lesions, resulting in a sensitivity of 81%, specificity of 78%, and overall accuracy of 81%. If the criterion was set higher at Cho SNR >4.0 the specificity improved to 89% but sensitivity was lowered to 67%.

Conclusion

The ROC analysis presented in this work could be used to set an objective diagnostic criterion depending on preferred emphasis on sensitivity or specificity. J. Magn. Reson. Imaging 2008;27:1114–1121. © 2008 Wiley‐Liss, Inc.
Voxel‐based diffusion tensor magnetic resonance imaging evaluation of low‐grade hepatic encephalopathy
Authors: Kumar Rajesh , Gupta Rakesh K. , Elderkin‐Thompson Virginia , Huda Amir , Sayre James , Kirsch Claudia , Guze Barry , Han Steve , Thomas M. Albert
Published: April 2008

Purpose

To quantify the changes in brain water diffusivity in hepatic encephalopathy (HE) associated with cirrhosis using diffusion tensor imaging (DTI) and to correlate with neuropsychological (NP) scores.

Materials and Methods

DTI was performed in 14 patients with low‐grade HE and age/gender‐comparable 16 healthy controls. Whole brain mean diffusivity (MD) and fractional anisotropy (FA) maps were calculated, normalized to common space, smoothed, and compared voxel‐by‐voxel between groups using analysis of covariance with age included as a covariate. The average MD and FA values were also calculated from individual subjects for selected brain regions and correlated with the neuropsychological scores.

Results

Patients with HE showed increased MD in the cortical gray and white matter and the internal capsule. Less extensive brain regions with decreased FA were observed in the bilateral frontal and occipital white matter. MD values from the corpus callosum correlated inversely with several NP scores among HE patients and controls. Positive correlations were observed with FA values and cognitive scores.

Conclusion

Voxel‐based DTI analysis showed widespread brain regions with increased MD values, indicating enhanced water content and decreased FA in cirrhotic patients with HE. The MD and FA values from selected regions correlated with the NP scores. J. Magn. Reson. Imaging 2008;27:1061–1068. © 2008 Wiley‐Liss, Inc.
Water excitation MPRAGE: An alternative sequence for postcontrast imaging of the abdomen in noncooperative patients at 1.5 Tesla and 3.0 Tesla MRI
Authors: Altun Ersan , Semelka Richard C. , Dale Brian M. , Elias Jorge
Published: April 2008

Purpose

To evaluate the diagnostic image quality of postgadolinium water excitation–magnetization‐prepared rapid gradient‐echo (WE‐MPRAGE) sequence in abdominal examinations of noncooperative patients at 1.5 Tesla (T) and 3.0T MRI.

Materials and Methods

Eighty‐nine consecutive patients (48 males and 41 females; mean age ± standard deviation, 54.6 ± 16.6 years) who had MRI examinations including postgadolinium WE‐MPRAGE were included in the study. Of 89 patients, 33 underwent noncooperative protocol at 1.5T, 10 underwent noncooperative protocol at 3.0T, and 46 underwent cooperative protocol at 3.0T. Postgadolinium WE‐MPRAGE, MPRAGE, and three‐dimensional gradient‐echo sequences of these three different groups were qualitatively evaluated for image quality, extent of artifacts, lesion conspicuity, and homogeneity of fat‐attenuation by two reviewers retrospectively, independently, and blindly. The results were compared using Wilcoxon signed rank and Mann‐Whitney U tests. Kappa statistics were used to measure the extent of agreement between the reviewers.

Results

The average scores indicated that the images were diagnostic for WE‐MPRAGE at 1.5T and 3.0T in noncooperative patients. WE‐MPRAGE achieved homogenous fat‐attenuation in 31/33 (94%) of noncooperative patients at 1.5T and 10/10 (100%) of noncooperative patients at 3.0T. WE‐MPRAGE at 3.0T had better results for image quality, extent of artifacts, lesion conspicuity and homogeneity of fat‐attenuation compared with WE‐MPRAGE at 1.5T, in noncooperative patients (P = 0.0008, 0.0006, 0.0024, and 0.0042; respectively). Kappa statistics varied between 0.76 and 1.00, representing good to excellent agreement.

Conclusion

WE‐MPRAGE may be used as a T1‐weighted postgadolinium fat‐attenuated sequence in noncooperative patients, particularly at 3.0T MRI. J. Magn. Reson. Imaging 2008;27:1146–1154. © 2008 Wiley‐Liss, Inc.
Automatic repositioning of MRSI voxels in longitudinal studies: Impact on reproducibility of metabolite concentration measurements
Authors: Ratai Eva‐Maria , Hancu Ileana , Blezek Daniel J. , Turk Katherine W. , Halpern Elkan , González R. Gilberto
Published: April 2008

Purpose

To study an automatic repositioning method to reduce variability in longitudinal MRSI exams based on a priori image registration. Longitudinal proton MR spectroscopic imaging (1H MRSI) exams to study the effects of disease or treatment are becoming increasingly common. However, one source of variability in such exams arises from imperfect relocalization of the MRSI grid in the follow‐up exams.

Materials and Methods

Six healthy subjects were each scanned three times during the course of 1 day. In each follow‐up exam a manually placed MRSI grid was acquired in addition to the automatically repositioned MRSI grid. Then coefficients of variance between baseline and follow‐up scans were calculated for N‐acetylaspartate, creatine, and choline. In addition, the overall MRSI grid overlap and individual voxel overlaps were also calculated for both the visually and automatically repositioned voxels.

Results

Streamlined workflow, reduced variability of metabolite concentration measurements, and increased voxel overlaps are noted when this automatic repositioning procedure is compared to the visual MRSI grid repositioning approach.

Conclusion

Our results suggest that this approach is able to improve reproducibility in longitudinal MRS exams. J. Magn. Reson. Imaging 2008;27:1188–1193. © 2008 Wiley‐Liss, Inc.
Climatology and impact on air quality of sea breeze in an urban coastal environment
Authors: Papanastasiou D. K. , Melas D.
Published: April 2008

The aims of this paper are to investigate the characteristics of the sea breeze that is developing in Volos area, a medium sized coastal city in central Greece, and to study the influence of sea breeze on concentration levels of ozone and PM10, during the period 2001–2005. The identification of sea breeze days is based on a set of strict, objective criteria, which include the wind direction and its diurnal reversal, the wind direction difference between the surface winds and the winds in the free atmosphere and the thermal contrast between the sea and the land surface. The statistical analysis reveals that sea breeze is developing in 85.6% of days from May until July, with maximum frequency of occurrence 89% in June. Its most frequent onset and cessation time periods are 09:00–11:00 and 20:00–22:00 LST respectively and its usual duration is approximately 10 h. The average maximum strength is 2.6 m/s, usually between 14:00 and 17:00 LST, while the maximum observed value equals 5.9 m/s. Studying the variation of ozone and PM10 levels during the cold and the warm period of the year (October–April and May–September respectively), it is concluded that sea breeze development is associated with an increase of the concentration of both pollutants. This increase is more pronounced during the cold period and is attributed to unfavourable meteorological conditions. Copyright © 2008 Royal Meteorological Society
Novel model for studying hematogenous infection in an experimental setting of implant‐related infection by a community‐acquired methicillin‐resistant S. aureus Strain
Authors: Poultsides Lazaros A. , Papatheodorou Loukia K. , Karachalios Theofilos S. , Khaldi Lubna , Maniatis Antonios , Petinaki Efthimia , Malizos Konstantinos N.
Published: April 2008

The aim of this study is to establish a new experimental model of hematogenous implant‐related infection (IRI) by a community‐acquired methicillin‐resistant S. aureus (CA‐MRSA) strain. Cylindrical porous tantalum intramedullary implants were inserted in the proximal right tibia of 30 male white rabbits after administration of antibiotic prophylaxis. Four weeks later and without antibiotic prophylaxis, 20 animals received 1 ml of inoculum of two different concentrations (study groups A and B) of CA‐MRSA strain through an ipsilatelar femoral artery catheter. The remaining 10 received normal saline instead (control group C). Surviving animals were sacrificed 4 weeks later. Sterile bone, bone marrow biopsies, and implants were harvested for culture and histological evaluation. Ten animals receiving 5 × 108cfu/ml (group A) died within 48–72 h due to septic shock. Blood cultures were positive; histology demonstrated acute infection. Ten animals received bacterial load of 3 × 108cfu/ml (group B) and all survived; two had negative Gram‐stain and cultures but PCR and RT‐PCR results demonstrated the viability of the microorganisms, while periprosthetic osteolysis and histological evaluation indicated subacute osteomyelitis; eight animals established periprosthetic infection, osteomyelitis, and septic arthritis documented by positive Gram‐stain, cultures, subperiosteal reaction, and chronic infection on histology. Control group specimens demonstrated no signs of infection. Histopathological semiquantitative scoring was used to compare the three groups. Comparison of groups A and B with control group and between group A and B showed statistically significant difference (p < 0.05) in all parameters except for periosteal reaction between groups B and C (p = 0.354). This novel, reproducible experimental model will facilitate the study of hematogenous CA‐MRSA IRIs. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1355–1362, 2008