bluuebunny/crossref_metadata_2025 huggingface dataset:
The Roles of T-Type Calcium Channel in the Development of Neuropathic Pain following Chronic Compression of Rat Dorsal Root Ganglia
Authors: Wen Xian-Jie , Xu Shi-Yuan , Chen Zhi-Xin , Yang Cheng-Xiang , Liang Hua , Li Heng
Published: May 2010

This study aimed to elucidate the role of T-type calcium channels in the nociceptive signal transmission at the spinal level. The chronic compression of dorsal root ganglion (CCD) rat model was adopted. Three doses (50, 100 and 200 µg in groups Mib50, Mib100 and Mib200, respectively) of specific T-type Ca2+ channel inhibitors mibefradil (Mib) or normal saline (NS) were intrathecally administered on the 5th day after the CCD model had been established. The paw withdrawal latency from a noxious thermal stimulus and paw withdrawal mechanical threshold of von Frey filament was used to measure the thermal hyperalgesia and tactile allodynia, respectively. Lumbar spinal cords of the rats isolated on the 5th day after the operation were prepared to measure the mRNA expression of T-type (Cav3.1, Cav3.2 and Cav3.3) calcium channel with RT-PCR methods. The results demonstrated that CCD rats produced reliable thermal hyperalgesia and tactile allodynia after surgery. The intrathecal administration of Mib significantly suppressed thermal hyperalgesia and allodynia in CCD rats (p< 0.01), and the inhibitory effect lasted for 2 h. However, only Cav3.2 and Cav3.3 T-type calcium channel mRNA were detected in the lumbar spinal cord of rats, and there were no Cav3.1 calcium channels. Compared with native and sham groups, the Cav3.2 and Cav3.3 calcium channel mRNA expression increased significantly (p < 0.05). These data support the view that spinal T-type calcium (Cav3.2 and Cav3.3 but not Cav3.1) channels may play an important role in the pathogenesis of neuropathic pain.
Cebus paraguayanus and Cebus nigritus (Primates, Platyrrhini): A Comparative Genomic Hybridization Analysis
Authors: Nieves M. , Mühlmann M. , Mudry M.D.
Published: May 2010

Primate genomes show a great karyological variability while the DNA content variation is scarce. The biggest genome size occurs in Cercophitecus cephus (Catarrhini, Cercophitecidae) with 5.26 pg whereas the smallest one is described for Callicebus torquatus (Platyrrhini, Callithricidae) with 2.26 pg. Over the last 20 years different authors have been studying the Platyrrhini genomes on a chromosomal level. Among them, Cebus (Cebidae) being considered the most ancestral and conserved karyotype in relation to human karyotype has been extensively studied. Cebus genome sizes range from 3.40 to 3.98 pg. The species that inhabit Argentina, where they reach the most southern natural distribution, Cebus paraguayanus (CPA) and Cebus nigritus (CNI), have been extensively studied with classical cytogenetic comparisons focusing on banding pattern behavior. In the present study we performed comparative genomic hybridization (CGH) between these two closely related species with the aim of going a step further in the dissection of Cebus genomes. CGH evidenced that the DNA imbalances between them involved different genome regions, i.e. preferentially repetitive DNA in CPA and coding or very disperse DNA in CNI. Particularly, CNI showed species-specific DNA in more than 9 chromosomal pairs with a red/green (r/g) ratio ranging from 1.7 to 4, meaning that CNI presents at least twice as much DNA than CPA in those chromosomal segments. CPA showed species-specific DNA in the telomeric region of at least 3 chromosomal pairs with an r/g ratio of 0.5. They also showed a DNA gain in the chromosomal pairs with extracentromeric heterochromatin. Our findings modify the widespread idea of considering the heterochromatin proportion as the only difference between CPA and CNI. In Cebus then, the diversification process could be mediated by little changes in DNA content accompanied by a euchromatin-heterochromatin interaction although maintaining a minimum proportion like the one observed in CNI.
Pediatric Atypical Spitzoid Neoplasms: A Review with Emphasis on ‘Red’ (‘Spitz’) Tumors and ‘Blue’ (‘Blitz’) Tumors
Authors: Ferrara Gerardo , Zalaudek Iris , Savarese Imma , Scalvenzi Massimiliano , Argenziano Giuseppe
Published: May 2010

Background: The diagnosis of pediatric atypical Spitz nevus/tumors (pASNT) is an emerging challenge in clinical dermatology and dermatopathology. Objective and Methods: We review the main clinicopathologic issues raised by pASNT and describe 2 examples of different clinicopathologic subsets of lesions. Results: While Spitz/Reed nevi are commonly small- to medium-sized, tan to black plaques, pASNT are large and nodular, either ‘red’ (dotted and/or polymorphous vascular pattern on dermoscopy; spindle and/or epithelioid tumors on histopathology: Spitz tumors, sensu strictiori) or ‘blue’ (homogeneous blue color on dermoscopy; intimate admixture of epithelioid cells and heavily pigmented dendritic cells on histopathology: Blitz tumors or pigmented epithelioid melanocytomas). Conclusions: Different clinicopathologic settings of pASNT probably exist. Dermoscopy can aid in their recognition and classification.
A Subtle Familial Translocation t(3;21)(p26.3;q22.3): An Apparently Healthy Boy with a 3p Deletion and 21q Duplication
Authors: Gijsbers A.C.J. , van Haeringen A. , Bosch C.A.J. , Hansson K. , Verschuren M. , Bakker E. , Breuning M.H. , Ruivenkamp C.A.L.
Published: May 2010

Here we report the clinical and cytogenetic results of a family carrying a cryptic translocation involving chromosome 3pter and 21qter detected by single nucleotide polymorphism array and subtelomeric fluorescent in situ hybridisation analysis. The index patient, with mild mental retardation in combination with minor dysmorphic features, inherited the derivative chromosome 21 resulting in a partial trisomy of the short arm of chromosome 3 and a partial monosomy of the long arm of chromosome 21. Her apparently healthy brother inherited the derivative chromosome 3 resulting in a terminal deletion of the short arm of chromosome 3 and a terminal duplication of the long arm of chromosome 21. We discuss the different phenotypes for the 2 genotypes and argue for the importance of reporting these imbalances to achieve accurate genetic counseling in prenatal and postnatal diagnosis.
Angiopoietin-1 Inhibits Mouse Glomerular Endothelial Cell Senescence via Tie2 Receptor-Modulated ERK1/2 Signaling
Authors: Yang Min , Zhang Minmin , Chen Jing , Mukherjee Rajarshi , Zhang Liyin , Lin Shanyan , Gu Yong
Published: May 2010

Background: The vasculature plays a key role in the progression of renal damage in aging, with reduction in glomerular and peritubular capillary density and decreased endothelial proliferative response. In this study, we examined the role of angiopoietin-1 (Ang1) in H2O2-induced senescence in mouse glomerular endothelial cells (MGECs) and the signaling pathway involved. Methods: MGECs were subjected to H2O2-induced senescence, which was evaluated by senescence-associated β-galactosidase (SA-β-Gal) staining, cell cycle analysis and expression of p16. Endothelial cell function was assessed by nitric oxide, von Willebrand factor secretion and capillary-like structure formation. Signal transduction was examined by Western blot with or without a specific inhibitor. Results: Ang1 significantly inhibited H2O2-induced senescence in MGECs, attenuated SA-β-Gal activity, resumed growth, and downregulated p16INK4a levels. Moreover, Ang1 regulated the secretion and capillary-like structure formation of endothelial cells with aging. However, these changes were markedly blocked by treatment with Ang2, sTie2-Fc and PD98059. Ang1 treatment markedly increased elevated Tie2 and ERK1/2 phosphorylation levels which were reduced by Ang2 and sTie2-Fc. PD98059 substantially reduced senescence while not altering Ang1-stimulated phosphor-Tie2 stimulation. Conclusion: The present studies suggest that Ang1 inhibits H2O2-induced senescence in MGECs via the Ang1–Tie2–ERK1/2 signaling pathway.
Impact of Altered Alveolar Volume on the Diffusing Capacity of the Lung for Carbon Monoxide in Obesity
Authors: Enache Irina , Oswald-Mammosser Monique , Scarfone Stéphanie , Simon Chantal , Schlienger Jean-Louis , Geny Bernard , Charloux Anne
Published: May 2010

Background: Studies on the diffusing capacity of the lung for carbon monoxide (DLCO) in obese patients are conflicting, some studies showing increased DLCO and others unaltered or reduced values in these subjects. Objectives: To compare obese patients to controls, examine the contribution of alveolar volume (VA) and CO transfer coefficient (KCO) to DLCO, and calculate DLCO values adjusted for VA. Methods: We measured body mass index (BMI), waist circumference (WC), spirometry and DLCO in 98 adult obese patients without cardiopulmonary or smoking history and 48 healthy subjects. All tests were performed in the same laboratory. Results: Using conventional reference values, mean DLCO and VA were lower (–6%, p < 0.05, and –13%, p < 0.001, respectively), and KCO was higher (+9%, p < 0.05) in obese patients than in controls. VA decreased whereas KCO increased with increasing BMI and WC in the obese group. Patients with lower DLCO had low KCO in addition to decreased VA. In contrast, some obese patients maintained normal VA, which, coupled with high KCO, resulted in higher DLCO. The main result is that diffusion capacity differences between obese patients and controls disappeared using reference equations adjusting DLCO for VA. Conclusions: Using conventional reference equations, our obese patients show slightly lower mean DLCO, lower mean VA and higher mean KCO than controls, but with a large range of DLCO values and patterns. Adjusting DLCO for VA suggests that low lung volumes are the main cause of low DLCO and high KCO values in obese patients.
Molecular Imaging of Atherosclerotic Plaques Targeted to Oxidized LDL Receptor LOX-1 by SPECT/CT and Magnetic Resonance
Authors: Li Dayuan , Patel Amit R. , Klibanov Alexander L. , Kramer Christopher M. , Ruiz Mirta , Kang Bum-Yong , Mehta Jawahar L. , Beller George A. , Glover David K. , Meyer Craig H.
Published: May 2010

Background—

The oxidized low-density lipoprotein receptor (LDLR) LOX-1 plays a crucial role in atherosclerosis. We sought to detect and assess atherosclerotic plaque in vivo by using single-photon emission computed tomography/computed tomography and magnetic resonance imaging and a molecular probe targeted at LOX-1.

Methods and Results—

Apolipoprotein E
−/−
mice fed a Western diet and LDLR
−/−
and LDLR
−/−
/LOX-1
−/−
mice fed an atherogenic diet were used. Imaging probes consisted of liposomes decorated with anti–LOX-1 antibodies or nonspecific immunoglobulin G,
111
indium or gadolinium, and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine fluorescence markers. In vivo imaging was performed 24 hours after intravenous injection (150 μL) of LOX-1 or nonspecific immunoglobulin G probes labeled with either
111
indium (600 μCi) or gadolinium (0.075 mmol/kg), followed by aortic excision for phosphor imaging and Sudan IV staining, or fluorescence imaging and hematoxylin/eosin staining. The LOX-1 probe also colocalized with specific cell types, apoptosis, and matrix metalloproteinase-9 expression in frozen aortic sections. Single-photon emission computed tomography/computed tomography imaging of the LOX-1 probe showed aortic arch “hot spots” in apolipoprotein E
−/−
mice (n=8), confirmed by phosphor imaging. Magnetic resonance imaging showed significant Gd enhancement in atherosclerotic plaques in LDLR
−/−
mice with the LOX-1 (n=7) but not with the nonspecific immunoglobulin G (n=5) probe. No signal enhancement was observed in LDLR
−/−
/LOX-1
−/−
mice injected with the LOX-1 probe (n=5). These results were confirmed by ex vivo fluorescence imaging. The LOX-1 probe bound preferentially to the plaque shoulder, a region with vulnerable plaque features, including extensive LOX-1 expression, macrophage accumulation, apoptosis, and matrix metalloproteinase-9 expression.

Conclusions—

LOX-1 can be used as a target for molecular imaging of atherosclerotic plaque in vivo. Furthermore, the LOX-1 imaging signal is associated with markers of rupture-prone atherosclerotic plaque.
Is the Myocardial Blush Grade Scored by the Operator During Primary Percutaneous Coronary Intervention of Prognostic Value in Patients With ST-Elevation Myocardial Infarction in Routine Clinical Practice?
Authors: Kampinga Marthe A. , Nijsten Maarten W.N. , Gu Youlan L. , Dijk W. Arnold , de Smet Bart J.G.L. , van den Heuvel Ad F.M. , Tan Eng-Shiong , Zijlstra Felix
Published: May 2010

Background—

Multiple trials have documented that myocardial blush grade (MBG) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) has prognostic value for long-term clinical outcome. However, to the best of our knowledge, no study has determined the clinical use of MBG in routine clinical practice. We determined the prognostic value of MBG scored by the operator during primary PCI in consecutive patients with STEMI.

Methods and Results—

The prognostic value of MBG scored by the operator in relation to 1-year all cause mortality was evaluated in all patients with STEMI who underwent primary PCI between January 2004 and July 2008 in our hospital. The incidence of MBG 0, 1, 2, and 3 was 12%, 14%, 36%, and 38%, respectively, in 2118 consecutive patients with STEMI. Follow-up of all 2118 patients showed a 1-year all cause mortality rate of 8% (168 of 2118): 24%, 10%, 6%, and 4%, respectively, among patients with MBG 0, 1, 2, and 3 (
P
<0.001). In the 1763 patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 after PCI, these mortality rates were 17%, 10%, 6%, and 4%, respectively (
P
<0.001). MBG scored by the operator was a strong independent predictor of 1-year all cause mortality corrected for other well-known predictive variables, including TIMI flow grade.

Conclusions—

MBG scored by the operator during primary PCI has prognostic value for 1-year all cause mortality in patients with STEMI in routine clinical practice. Therefore, the MBG should be documented, in addition to the TIMI flow grade, during primary PCI in patients with STEMI in standard PCI reports in routine clinical practice.
“A Fine Romance”: The Courtship Correspondence between Louisa Catherine Johnson and John Quincy Adams
Authors: Heffron Margery M.
Published: May 2010

Before they married in July 1797, Louisa Catherine Johnson and John Quincy Adams conducted a stormy correspondence that previewed their fifty-year marriage. The exceptional strengths they shared—wit, ambition, courage in adversity—would sustain them through devastating family tragedies but could not ease their path through a painful courtship.
Karl Marx between Two Worlds: The Antinomies of Giovanni Arrighi’s Adam Smith in Beijing
Authors: Walker Richard
Published: May 2010

Adam Smith in Beijing is a huge and sprawling book, but Giovanni Arrighi has done a great service with his world-historical vision of today’s capitalism and the growing rivalry between a fading American empire and the rising power of China. This is a task beyond most of us, and one bound to put the writer at risk of criticism from many quarters. The book shines in two regards. One is to make geographical dynamics central to world-history ‐ which means seeing the global economy as more than the sum of development-histories of many places or, worse, the spread of capitalism from one country to another. A second virtue is embedding economic history in the politics of the international state-system, featuring the use of force, imperial expansion, and the role of hegemonic powers. Nevertheless, Arrighi’s economic-geographic analysis fails to convince on a number of critical points, such as the origins of industrial revolution, why Europe overtook China in early modern times, why the US economy faltered after 1970, why finance has run amuck in our time, how Japan grew so enormously after World War II, or why China is expanding so prodigiously today.
Giovanni Arrighi in Beijing: An Alternative to Capitalism?
Authors: Panitch Leo
Published: May 2010

Giovanni Arrighi made a remarkably broad-ranging and original contribution to comparative political economy and historical sociology over five decades. His last book shares these qualities. But Adam Smith in Beijing is unfortunately not mainly about the origins and dynamics of Chinese capitalism over the past three decades. It presents Adam Smith not as the apostle of free-market capitalism, but rather of a ‘non-capitalist market society’; and it uses this to make the case that since China’s economic development takes place outside the European/North American capitalist ‘core’, it must, almost by definition, not be capitalist. Markets are conceived here as the instruments of states, yet the theory of the state advanced is severely undeveloped. Arrighi’s argument that China’s economic development is part and parcel of the demise of the US project for establishing itself as the ‘world state’ misinterprets the nature of the US empire as well as misses the extent of China’s integration with US-led capitalist globalisation.
Arrighi’s Adam Smith in Beijing: Engaging China
Authors: Flemming Christiansen
Published: May 2010

This contribution examines Arrighi’s effort in Adam Smith in Beijing to understand the trajectory of China’s political economy and the effects of that trajectory on the current reforms and changes in China. This article discusses these reforms from the perspective of China’s ’internal’ dynamics and suggests that Arrighi’s argument has been developed without proper reference to China’s complex realities. As an alternative, the contribution proposes a research-agenda that could better account for these realities.
The Degradation of the International Legal Order? The Rehabilitation of Law and the Possibility of Politics, Bill Bowring, Routledge-Cavendish, 2008
Authors: Knox Robert J.
Published: May 2010

Bill Bowring’s book attempts to argue for a Marxist account of international law that embraces it as a tool for progressive politics and revolutionary change. He argues it is necessary to give a substantive account of both, locating them in the real struggles of the oppressed. Specifically, he locates human rights in the three great revolutions ‐ the French, the Russian and the anticolonial. However, this revolutionary heritage has been ‘degraded’ by recent events. As such, it is necessary to adopt ‘revolutionary conservatism’, invoking international law’s origins against its current degradation. This review argues that, owing to international law’s indeterminacy, Bowring’s project is susceptible to imperial appropriation. This means, however, that Bowring cannot give an account of why we should use international law. It then argues that Bowring’s account of Pashukanis is wrong, and that Pashukanis’s work can better make sense of Bowring’s insights and international law more generally.
Object Recognition in 3D Point Clouds Using Web Data and Domain Adaptation
Authors: Lai Kevin , Fox Dieter
Published: May 2010

In recent years, object detection has become an increasingly active field of research in robotics. An important problem in object detection is the availability of a sufficient amount of labeled training data to learn good classifiers. In this paper we show how to significantly reduce the need for manually labeled training data by leveraging data sets available on the World Wide Web. Specifically, we show how to use objects from Google’s 3D Warehouse to train an object detection system for 3D point clouds collected by robots navigating through both urban and indoor environments. In order to deal with the different characteristics of the web data and the real robot data, we additionally use a small set of labeled point clouds and perform domain adaptation . Our experiments demonstrate that additional data taken from the 3D Warehouse along with our domain adaptation greatly improves the classification accuracy on real-world environments.
Alienation, Servility and Amorality: Relating Gogol’s Portrayal of Bureaupathology to an Accountability Era
Authors: Samier Eugenie , Lumby Jacky
Published: May 2010

This article explores the insights literature can bring to administrative and bureaucratic critique, focusing on the work of Nikolai Gogol. Gogol’s satire of bureaucracy presages many subsequent social science analyses. These encompass the fundamental ruptures in society caused by a surfeit of bureaucracy in ‘The Nose’ and, on a more psychological level, the effects of bureaucratization on the individual in ‘The Overcoat’. His stories portray the alienation, futile activity and servility caused in lower level functionaries through problems of loss of identity, the absence of meaningful work and a lack of separation between public and private life. This article uses Gogol’s work to intensify and sharpen an exploration of the pathological responses of educational administrators and policy makers to an accountability era of burgeoning bureaucracy that has a profound negative impact on performance.
miR-28 is a thrombopoietin receptor targeting microRNA detected in a fraction of myeloproliferative neoplasm patient platelets
Authors: Girardot Michael , Pecquet Christian , Boukour Siham , Knoops Laurent , Ferrant Augustin , Vainchenker William , Giraudier Stéphane , Constantinescu Stefan N.
Published: May 2010

BCR-ABL negative myeloproliferative neoplasms (MPNs; polycythemia vera, essential thrombocythemia, primary myelofibrosis) are malignant diseases arising from a multipotent hematopoietic progenitor, frequently altered by JAK2 V617F or other JAK/STAT activating mutations. The thrombopoietin receptor (TpoR, MPL) is one of the major dimeric cytokine receptors that use JAK2 in the myeloid lineage, and was found to be down-modulated in certain MPN patients. We searched for negative regulators of MPL expression. Here we report that miR-28 targets the 3′ untranslated (3′UTR) region of MPL, inhibiting its translation, as well as other proteins potentially involved in megakaryocyte differentiation, such as E2F6. Expression of miR-28 in CD34-derived megakaryocytes inhibited terminal differentiation. miR-28 was found to be overexpressed in platelets of a fraction of MPN patients, while it was expressed at constant low levels in platelets from healthy subjects. Constitutive activation of STAT5 leading to autonomous growth of hematopoietic cell lines was associated with increased miR-28 expression. We discuss how down-modulating MPL and other targets of miR-28, and of related miR-708 and miR-151, could contribute to MPN pathogenicity.
The inositol phosphatase SHIP-1 is negatively regulated by Fli-1 and its loss accelerates leukemogenesis
Authors: Lakhanpal Gurpreet K. , Vecchiarelli-Federico Laura M. , Li You-Jun , Cui Jiu-Wei , Bailey Monica L. , Spaner David E. , Dumont Daniel J. , Barber Dwayne L. , Ben-David Yaacov
Published: May 2010

The activation of Fli-1, an Ets transcription factor, is the critical genetic event in Friend murine leukemia virus (F-MuLV)–induced erythroleukemia. Fli-1 overexpression leads to erythropoietin-dependent erythroblast proliferation, enhanced survival, and inhibition of terminal differentiation, through activation of the Ras pathway. However, the mechanism by which Fli-1 activates this signal transduction pathway has yet to be identified. Down-regulation of the Src homology 2 (SH2) domain-containing inositol-5-phosphatase-1 (SHIP-1) is associated with erythropoietin-stimulated erythroleukemic cells and correlates with increased proliferation of transformed cells. In this study, we have shown that F-MuLV–infected SHIP-1 knockout mice display accelerated erythroleukemia progression. In addition, RNA interference (RNAi)-mediated suppression of SHIP-1 in erythroleukemia cells activates the phosphatidylinositol 3-kinase (PI 3-K) and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathways, blocks erythroid differentiation, accelerates erythropoietin-induced proliferation, and leads to PI 3-K–dependent Fli-1 up-regulation. Chromatin immunoprecipitation and luciferase assays confirmed that Fli-1 binds directly to an Ets DNA binding site within the SHIP-1 promoter and suppresses SHIP-1 transcription. These data provide evidence to suggest that SHIP-1 is a direct Fli-1 target, SHIP-1 and Fli-1 regulate each other in a negative feedback loop, and the suppression of SHIP-1 by Fli-1 plays an important role in the transformation of erythroid progenitors by F-MuLV.
Bioinformatic prediction, deep sequencing of microRNAs and expression analysis during phenotypic plasticity in the pea aphid, Acyrthosiphon pisum
Authors: Legeai Fabrice , Rizk Guillaume , Walsh Thomas , Edwards Owain , Gordon Karl , Lavenier Dominique , Leterme Nathalie , Méreau Agnès , Nicolas Jacques , Tagu Denis , Jaubert-Possamai Stéphanie
Published: May 2010

Background

Post-transcriptional regulation in eukaryotes can be operated through microRNA (miRNAs) mediated gene silencing. MiRNAs are small (18-25 nucleotides) non-coding RNAs that play crucial role in regulation of gene expression in eukaryotes. In insects, miRNAs have been shown to be involved in multiple mechanisms such as embryonic development, tissue differentiation, metamorphosis or circadian rhythm. Insect miRNAs have been identified in different species belonging to five orders: Coleoptera, Diptera, Hymenoptera, Lepidoptera and Orthoptera.

Results

We developed high throughput Solexa sequencing and bioinformatic analyses of the genome of the pea aphid Acyrthosiphon pisum in order to identify the first miRNAs from a hemipteran insect. By combining these methods we identified 149 miRNAs including 55 conserved and 94 new miRNAs. Moreover, we investigated the regulation of these miRNAs in different alternative morphs of the pea aphid by analysing the expression of miRNAs across the switch of reproduction mode. Pea aphid microRNA sequences have been posted to miRBase: http://microrna.sanger.ac.uk/sequences/

Conclusions

Our study has identified candidates as putative regulators involved in reproductive polyphenism in aphids and opens new avenues for further functional analyses.
Prognostic utility of chromosomal instability detected by fluorescence in situ hybridization in fine-needle aspirates from oral squamous cell carcinomas
Authors: Sato Hiroaki , Uzawa Narikazu , Takahashi Ken-Ichiro , Myo Kunihiro , Ohyama Yoshio , Amagasa Teruo
Published: May 2010

Background

Although chromosomal instability (CIN) has been detected in many kinds of human malignancies by means of various methods, there is no practical assessment for small clinical specimens. In this study, we evaluated CIN in fine-needle aspiration (FNA) biopsied oral squamous cell carcinomas (SCCs) using fluorescence in situ hybridization (FISH) analysis, and investigated its prognostic significance.

Methods

To evaluate CIN status of tumors, FISH with genomic probes for the centromeres of chromosomes 7, 9, and 11 was performed on specimens obtained by FNA from 77 patients with primary oral SCCs.

Results

High-grade CIN (CIN3) was observed in 11.7% (9/77) of patients with oral SCCs and was associated significantly with reduced disease-free survival (p = .008) and overall survival (p = .003). Multivariate Cox proportional hazards analysis showed that CIN status was significantly correlated with disease-free survival (p = .035) and overall survival (p = .041).

Conclusion

Analysis of CIN status using FISH on FNA biopsy specimens may be useful in predicting of recurrence and poor prognosis in patients with oral SCCs.
Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci
Authors: Berg Marianne , Ågesen Trude H , Thiis-Evensen Espen ,   [the INFAC-study group], Merok Marianne A , Teixeira Manuel R , Vatn Morten H , Nesbakken Arild , Skotheim Rolf I , Lothe Ragnhild A
Published: May 2010

Background

Estimates suggest that up to 30% of colorectal cancers (CRC) may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV) (Roche NimbleGen, 385 000 oligo CGH array) in microsatellite stable (MSS) tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53) and 17 elderly patients with median age 79 years (range: 69-87). Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list.

Results

The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups.

Conclusions

Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late onset CRC. Integration of genome and transcriptome data identifies seven novel candidate genes with the potential to identify an increased risk for CRC.
A study on the applicability of implantable microchip transponders for body temperature measurements in pigs
Authors: Lohse Louise , Uttenthal Åse , Enøe Claes , Nielsen Jens
Published: May 2010

Background

The applicability of an electronic monitoring system using microchip transponders for measurement of body temperatures was tested in 6-week-old conventional Danish weaners infected with classical swine fever virus (CSFV). Subcutaneous tissue temperatures obtained by the implantable transponders were compared with rectal temperatures, recorded by a conventional digital thermometer.

Methods

In a preliminary study, transponders were inserted subcutaneously at 6 different positions of the body of 5 pigs. The transponders positioned by the ear base provided the best correlation to rectal temperature. To test the stability of the monitoring system in a larger group of pigs, transponders were therefore inserted by the left ear base in a subsequent infection experiment with 30 pigs.

Results

Generally, the microchip transponders measured a subcutaneous tissue temperature, which was about 1°C lower than the rectal temperature. However, a simple linear relationship between the measures of the two methods was found.

Conclusions

Our study showed that the tested body monitoring system may represent a promising tool to obtain an approximate correlate of body temperatures in groups of pigs. In contrast, however, the tested system did not constitute a suitable tool to measure body temperatures of individual animals in the present pig infection experiment.
Seven-year follow-up of infliximab therapy in rheumatoid arthritis patients with severe long-standing refractory disease: attrition rate and evolution of disease activity
Authors: Vander Cruyssen Bert , Durez Patrick , Westhovens Rene , De Keyser Filip
Published: May 2010

Introduction

This study is based on the results from a Belgian expanded access program in which patients with active refractory and erosive rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab in combination with methotrexate. The objectives of this study were to evaluate the continuation rate of infliximab and its clinical effect over a 7-year period and to document the reasons for discontinuation.

Methods

Between 2000 and 2001, 511 patients with severe and refractory RA were enrolled and treated with infliximab. After 7 years, apart from routine clinical follow-up, treating rheumatologists were asked to complete a questionnaire designed specifically for the present study to evaluate the current therapy with infliximab, the level of disease activity (Disease Activity Score in 28 joints [DAS28]) and the reasons for infliximab discontinuation.

Results

After 7 years, 160 of 511 patients (31%) were still on infliximab treatment. The major reasons for infliximab discontinuation included lack of efficacy (104 patients), adverse events (107 patients) and elective change of therapy (70 patients). The majority of cases of treatment discontinuation for safety reasons occurred during the first 2 years. In contrast, discontinuation due to ineffectiveness showed a more constant rate over the 7-year period. Mean DAS for patients still on treatment with infliximab decreased from 5.7 (standard error [SE] 0.1) at baseline to 3.0 (SE 0.1) at year 4 and remained that low until year 7 (3.0 [SE 0.1]). Low disease activity (defined as DAS28 <3.2) was present in 60.9% of patients, and 45.5% achieved remission (DAS28 <2.6). DAS28 at the time of treatment discontinuation due to ineffectiveness decreased over the 7-year period from 5.6 (SE 0.3) in 2001 to 4.8 (SE 0.3) in 2008.

Conclusions

This observational study revealed that patients who continue to receive infliximab experience sustained clinical benefit. The majority of safety issues occurred during the first 2 years of infliximab therapy. We observed that the DAS at the time of therapy discontinuation showed a trend to decrease over time.
Endothelial cell markers reflecting endothelial cell dysfunction in patients with mixed connective tissue disease
Authors: Soltesz Pal , Bereczki Daniel , Szodoray Peter , Magyar Maria T , Der Henrietta , Csipo Istvan , Hajas Agota , Paragh Gyorgy , Szegedi Gyula , Bodolay Edit
Published: May 2010

Introduction

The aim of the present study was to investigate the association between cardiovascular risk factors and endothelial dysfunction in patients with mixed connective tissue disease (MCTD) and to determine which biomarkers are associated with atherosclerotic complications, such as cardiovascular disease.

Methods

Fifty MCTD patients and 38 healthy age-matched and sex-matched controls were enrolled in this study. In order to describe endothelial dysfunction, we assessed flow-mediated dilation (FMD), nitrate-mediated dilation (NMD) and carotid artery intima-media thickness (IMT). We investigated FMD of the brachial artery after reactive hyperemia and NMD after sublingual nitroglycerin administration, while the IMT of the common carotid artery was determined by ultrasound. Anti-U1 ribonucleoprotein (anti-U1RNP) antibodies, anti-cardiolipin (anti-CL) antibodies, anti-endothelial cell antibody (AECA) and endothelial cell markers, such as soluble thrombomodulin (TM) and von Willebrand factor antigen (vWFAg), were assessed.

Results

The endothelium-dependent vasodilation (FMD) was significantly impaired in patients with MCTD, as compared with controls (%FMD: 4.7 ± 4.2% vs. 8.7 ± 5.0%; P < 0.001), while the percentage NMD did not differ (%NMD: 14.3 ± 6.6% vs. 17.1 ± 6.7%; P = 0.073). Mean carotid IMT values were higher in patients than in controls (IMT: MCTD, 0.64 ± 0.13 mm vs. controls, 0.53 ± 0.14 mm; P < 0.001). FMD negatively correlated with disease duration, the levels of apolipoprotein A1, the paraoxonase-1 activity, and systolic blood pressure in MCTD patients. The percentage FMD was significantly lower in MCTD patients with cardiovascular diseases (CVD), than in those without CVD (%FMD: 3.5 ± 2.9 vs. 5.8 ± 4.8, P < 0.0002), while percentage NMD did not differ between patients with and without CVDs. Serum levels of autoantibodies (anti-U1RNP, AECA and anti-CL) were significantly higher in MCTD patients and differed between MCTD patients with and without CVD. Endothelial cell markers such as soluble TM (12.2 ± 8.1 ng/ml vs. 3.2 ± 1.3 ng/ml; P < 0.001) and vWFAg (224.1 ± 115% vs. 89.4 ± 27.1%, P < 0.001) were the highest in MCTD patients with CVD.

Conclusions

FMD is a reliable sensitive marker of endothelial cell dysfunction in MCTD. Beside the traditional risk factors, anti-U1RNP, AECA and anti-CL antibodies may be important not only in the pathogenesis of MCTD but in the induction of endothelial cell activation, and may play crucial roles in the development of early atherosclerosis in MCTD.
Reepithelialization of the Uterine Surface Arises from Endometrial Glands: Evidence from a Functional Mouse Model of Breakdown and Repair
Authors: Kaitu'u-Lino Tu'uhevaha J. , Ye Louie , Gargett Caroline E.
Published: May 2010

The human endometrium is highly regenerative undergoing monthly cycles of growth and regression. Endometrial repair after menses is a critical component of the cycle; however, little is understood about the mechanisms behind this rapid process. Adult stem/progenitor cells identified in human and mouse endometrium may be responsible for its remarkable regenerative capacity; however, a functional role for stem/progenitor cells in menstruation is yet to be established. This study aimed to identify label retaining cells as candidate epithelial stem or progenitor cells involved in the rapid reepithelization of the uterine surface in our functional mouse model of endometrial breakdown and repair. Adult mice were pulse labeled with bromodeoxyuridine before endometrial breakdown and repair was induced. Throughout endometrial breakdown and repair, very rapid dilution of bromodeoxyuridine label was observed in the luminal epithelium, whereas label within the glandular epithelium remained constant. Importantly, glandular epithelial cells were shown to proliferate selectively in response to endometrial repair, and the majority strongly expressed estrogen receptor-α at this time. This is the first study to demonstrate a functionally diverse response during endometrial repair from the anatomically connected luminal and glandular epithelium and highlights the likelihood that the endometrial glands are the residence of epithelial progenitor cells contributing to reepithelialization of the uterine surface after menses.
Ethnic Differences in Insulin Action in Obese African-American and Latino Adolescents
Authors: Hasson Rebecca E. , Adam Tanja C. , Davis Jaimie N. , Weigensberg Marc J. , Ventura Emily E. , Lane Christianne J. , Roberts Christian K. , Goran Michael I.
Published: May 2010

Introduction: African-American children have a greater acute insulin response to iv glucose (AIR) compared with Latino children despite a similar degree of insulin resistance and body composition. It is unclear whether African-Americans demonstrate an exaggerated insulin response to an oral glucose challenge and whether any differences are seen in more obese children in advanced pubertal development.

Purpose: Our objective was to compare glucose and insulin indices derived from an oral glucose tolerance test (OGTT) and iv glucose tolerance test (IVGTT) in sedentary, obese African-American (n = 59) and Latino (n = 83) adolescents.

Methods: Glucose and insulin incremental area under the curve was measured during an OGTT, and AIR, insulin sensitivity, disposition index, and glucose effectiveness were assessed during an IVGTT. Body composition was assessed via dual-energy x-ray absorptiometry and magnetic resonance imaging.

Results: From the OGTT, glucose and insulin IAUC were 29.1 and 22.5% lower (P = 0.01) in African-Americans compared with Latino adolescents. From the IVGTT, insulin sensitivity and glucose effectiveness were 41.7% (P < 0.01) and 50.0% (P = 0.02) lower in African-Americans compared to Latinos. AIR (P = 0.001) and disposition index (P = 0.02) were 63.0 and 48.8% higher in African-Americans, respectively, compared with Latinos. These findings persisted after controlling for body composition and fat distribution.

Conclusions: There were marked differences in glucose and insulin indices derived from the OGTT and IVGTT. African-Americans were more insulin resistant as measured by the IVGTT compared with the Latino adolescents. However, the well-described hyperinsulinemia in response to iv glucose was not observed after oral glucose in African-American adolescents.
Inhibition of Protein Kinase Cβ Does Not Improve Endothelial Function in Type 2 Diabetes
Authors: Beckman Joshua A. , Goldfine Allison B. , Goldin Alison , Prsic Adnan , Kim Sora , Creager Mark A.
Published: May 2010

Context: Antagonism of protein kinase Cβ (PKCβ) restores endothelial function in experimental models of diabetes and prevents vascular dysfunction in response to hyperglycemia in healthy humans.

Objective: We tested the hypothesis that PKCβ antagonism would improve vascular function in subjects with type 2 diabetes compared with healthy control subjects.

Design: The effect of PKCβ was evaluated in a randomized, placebo-controlled, double-blinded crossover trial.

Setting: The study was performed in the outpatient setting of a university medical center.

Participants: Thirteen subjects with type 2 diabetes without evidence of cardiovascular disease and 15 healthy control subjects were recruited via newspaper advertisement.

Intervention: Subjects underwent a randomized, double-blind, crossover, placebo-controlled trial of the selective PKCβ antagonist ruboxistaurin mesylate. Subjects received each treatment for 14 d.

Main Outcome Measure: Endothelium-dependent and endothelium-independent vasodilation of forearm resistance vessels was measured with mercury-in-silastic, strain-gauge plethysmography during intraarterial administration of methacholine chloride and verapamil, respectively. Markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress were measured after each treatment.

Results: Endothelium-dependent vasodilation of forearm resistance vessels was attenuated in diabetic subjects when compared with healthy subjects (P = 0.001). Endothelium-independent vasodilation did not differ between groups (P value not significant). Ruboxistaurin did not significantly change endothelium-dependent or endothelium-independent vasodilation or blood-based markers of inflammation, fibrinolysis, endothelial damage, and oxidative stress in either diabetic or healthy subjects.

Conclusion: Endothelial dysfunction of forearm resistance vessels was not improved by 2 wk of selective PKCβ inhibition in patients with diabetes. These results suggest that PKCβ does not contribute significantly to vascular dysfunction in otherwise healthy patients with type 2 diabetes.
Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast
Authors: Meitinger Franz , Petrova Boryana , Lombardi Ilde Mancini , Bertazzi Daniela Trinca , Hub Birgit , Zentgraf Hanswalter , Pereira Gislene
Published: May 2010

The mitotic-exit network (MEN) is a signaling pathway that is essential for the coordination of mitotic exit and cytokinesis. Whereas the role of the MEN in mitotic exit is well established, the molecular mechanisms by which MEN components regulate cytokinesis remain poorly understood. Here, we show that the MEN controls components involved in septum formation, including Inn1, Cyk3 and Chs2. MEN-deficient mutants, forced to exit mitosis as a result of Cdk1 inactivation, show defects in targeting Cyk3 and Inn1 to the bud-neck region. In addition, we found that the chitin synthase Chs2 did not efficiently localize at the bud neck in the absence of MEN activity. Ultrastructural analysis of the bud neck revealed that low MEN activity led to unilateral, uncoordinated extension of the primary and secondary septa. This defect was partially suppressed by increased levels of Cyk3. We therefore propose that the MEN directly controls cytokinesis via targeting of Inn1, Cyk3 and Chs2 to the bud neck.
Chelation-assisted carbonylation reactions catalyzed by Rh and Ru complexes
Authors: Chatani Naoto , Inoue Satoshi , Yokota Kazuhiko , Tatamidani Hiroto , Fukumoto Yoshiya
Published: May 2010

This account reviews chelation-assisted carbonylation reactions catalyzed by late transition metals. New carbonylation reactions are achieved with these catalysts in the presence of pyridin-2-ylmethanol and pyridin-2-ylmethylamine. The reactions involve activation of O-H and N-H bonds, coordination of the pyridine nitrogen to Rh being essential for the reaction to proceed. In addition, a new type of carbonylation of the ortho C-H bonds in aromatic amides in which the pyridin-2-ylmethylamino moiety functions as a bidentate directing group, is demonstrated. In this reaction, a dinuclear ruthenium complex was isolated from a stoichiometric reaction of amide and Ru3(CO)12, in which amide binds to one Ru atom in the expected N,N fashion and the carbonyl oxygen binds to the other Ru atom as an O-donor. These studies indicate that chelation methodology is useful for new types of carbonylation reaction, which cannot be achieved by non-chelation systems.
Catalytic activation of hydrogen, silicon, and fluorine by transition-metal complexes
Authors: Rauf Waqar , Hazari Amaruka , Gouverneur Véronique , Brown John M.
Published: May 2010

The remarkable versatility of palladium catalysis is exemplified by recent work in two distinct areas. Firstly, coupling chemistry is discussed, in which the reactive entity is generated by cleavage of a C–H or C–Si bond. The second part concerns the activation of allylic C–F bonds, where divergence from the normal stereochemical pattern of the reaction was observed.
Abstinence and Teenagers: Prevention Counseling Practices of Health Care Providers Serving High‐Risk Patients in the United States
Authors: Harper Cynthia C. , Henderson Jillian T. , Schalet Amy , Becker Davida , Stratton Laura , Raine Tina R.
Published: May 2010

CONTEXT: Abstinence‐only education has had little demonstrable impact on teenagers' sexual behaviors, despite significant policy and funding efforts. Given the struggle over resources to improve teenagers' reproductive health outcomes, the views of clinicians serving teenagers at high risk for unintended pregnancy and STDs merit particular attention.

METHODS: In 2005, a qualitative study with 31 clinicians serving low‐income, at‐risk patients was conducted.

A semistructured interview guide was used to ask clinicians about adolescent pregnancy, HIV and STD prevention counseling, and when they include abstinence. Thematic content analysis was used to examine the content of the counseling and the techniques used in different situations.

RESULTS: Providers reported offering comprehensive counseling, presenting abstinence as a choice for teenagers, along with information about contraceptives and condoms. Several providers mentioned that with young, sexually inexperienced teenagers, they discuss delaying sexual activity and suggest other ways to be affectionate, while giving information on condoms. Providers explained how they assess whether teenagers feel ready to be sexually active and try to impart skills for healthy relationships. Some described abstinence as giving teenagers a way to opt out of unwanted sexual activity. Many support abstinence if that is the patient's desire, but routinely dispense condoms and contraceptives.

CONCLUSIONS: Overall, providers did not give abstinence counseling as a rigid categorical concept in their preventive practices, but as a health tool to give agency to teenagers within a harm reduction framework. Their approach may be informative for adolescent policies and programs in the future.