bluuebunny/crossref_metadata_2025 huggingface dataset:
A C-terminal amino acid substitution in the γ-chain caused by a novel heterozygous frameshift mutation (Fibrinogen Matsumoto VII) results in hypofibrinogenaemia
Authors: Haneishi Ayumi , Yamauchi Kazuyoshi , Terasawa Fumiko , Ito Toshiro , Ishida Fumihiro , Okumura Nobuo , Fujihara Noriko
Published: June 2010

We found a novel hypofibrinogenemia designated as Matsumoto VII (M-VII), which is caused by a heterozygous nucleotide deletion at position g.7651 in FGG and a subsequent frameshift mutation in codon 387 of the γ-chain. This frameshift results in 25 amino acid substitutions, late termination of translation with elongation by 15 amino acids, and the introduction of a canonical glycosylation site. Western blot analysis of the patient’s plasma fibrinogen visualised with anti-γ-chain antibody revealed the presence of two extra bands. To identify the extra bands and determine which of the above-mentioned alterations caused the assembly and/or secretion defects in the patient, 11 variant vectors that introduced mutations into the cDNA of the γ-chain or γ′-chain were transfected into Chinese hamster ovary cells. In vitro expression of transfectants containing γΔ7651A and γΔ7651A/399T (γΔ7651A with an amino acid substitution of 399Asn by Thr and a variant lacking the canonical glycosylation site) demonstrated a reduction in secretion to approximately 20% of the level seen in the transfectants carrying the normal γ-chain. Furthermore, results from other transfectants demonstrated that eight aberrant residues between 391 and 398 of the M-VII variant, rather than the 15 amino acid extension or the additional glycosylation, are responsible for the reduced levels of assembly and secretion of M-VII variant fibrinogen. Finally, the results of this study and our previous reports demonstrate that the fibrinogen γ-chain C-terminal tail (388–411) is not necessary for protein assembly or secretion, but the aberrant amino acid sequence observed in the M-VII variant (especially 391–398) disturbs these functions.
mRNA levels of CD31, CD144, CD146 and von Willebrand factor do not serve as surrogate markers for circulating endothelial cells
Authors: Strijbos Michiel , van Krimpen Brigitte , Debets Reno , Kraan Jaco , Sleijfer Stefan , Gratama Jan Willem , Lamers Cor
Published: June 2010

Circulating endothelial cells (CEC) are considered a promising marker to determine the extent of vascular damage. However, currently available and validated CEC enumeration assays are laborious, time consuming and costly, which limits their clinical utility. Here, we evaluated the feasibility of quantifying mRNA levels of the endothelium-associated markers CD31, CD144, CD146 and von Willebrand factor (vWf) in peripheral blood (PB) of healthy donors, patients, and human umbilical veins by real-time reverse transcriptase polymerase chain reaction (RTPCR) and their use as surrogate markers for CEC. Whole blood samples and CD146+ cell-enriched fractions were assessed for mRNA and protein expression of CD31, CD144, CD146 and vWf by RT-PCR and flow cytometry, respectively. We showed the feasibility to detect endothelial mRNA isolated from HUVEC numbers as low as 10. However, no endothelial mRNA could be measure in whole blood samples, and only low levels of CD31 and CD146 mRNA were detected in suspensions of isolated CEC with numbers up to 4,450 CEC per sample. We conclude that mRNA levels of CD31, CD144, CD146 and vWf in whole blood as detected by real time RT-PCR cannot be used as biomarkers for endstage endothelial cells such as CEC.
Thrombogenesis with continuous blood flow in the inferior vena cava
Authors: Hawley Angela , Alvarado Christine , Berguer Alexandra , Baker Nichole , Wrobleski Shirley , Wakefield Thomas , Lucchesi Benedict , Myers Daniel , Diaz José
Published: June 2010

Several rodent models have been used to study deep venous thrombosis (DVT). However, a model that generates consistent venous thrombi in the presence of continuous blood flow, to evaluate therapeutic agents for DVT, is not available. Mice used in the present study were wild-type C57BL/6 (WT), plasminogen activator inhibitor-1 (PAI-1) knock out (KO) and Delta Cytoplasmic Tail (ΔCT). An electrolytic inferior vena cava (IVC) model (EIM) was used. A 25G stainless-steel needle, attached to a silver coated copper wire electrode (anode), was inserted into the exposed caudal IVC. Another electrode (cathode) was placed subcutaneously. A current of 250 μAmps over 15 minutes was applied. Ultrasound imaging was used to demonstrate the presence of IVC blood flow. Analyses included measurement of plasma soluble P-selectin (sP-Sel), thrombus weight (TW), vein wall morphometrics, P-selectin and Von Willebrand factor (vWF) staining, transmission electron microscopy (TEM), scanning electron microscopy (SEM); and the effect of enoxaparin on TW was evaluated. A current of 250 μAmps over 15 minutes consistently promoted thrombus formation in the IVC. Plasma sPSel was decreased in PAI-1 KO and increased in ΔCT vs. WT (WT/PAI-1: p=0.003, WT/ΔCT: p=0.0002). Endothelial activation was demonstrated by SEM, TEM, P-selectin and vWF immunohistochemistry and confirmed by inflammatory cell counts. Ultrasound imaging demonstrated thrombus formation in the presence of blood flow. Enoxaparin significantly reduced the thrombus size by 61% in this model. This EIM closely mimics clinical venous disease and can be used to study endothelial cell activation, leukocyte migration, thrombogenesis and therapeutic applications in the presence of blood flow.
Integrins on neutrophils are dispensable for migration into three-dimensional fibrin gels
Authors: Koenderman Leo , van der Linden Jan , Honing Henk , Ulfman Laurien
Published: June 2010

The innate immune system and the blood haemostasis system function cooperatively in many pathological conditions such as acute respiratory distress syndrome, deep venous thrombosis, ischaemia/reperfusion injury and cardiovascular disease. Infiltration of neutrophils into thrombotic substrates such as fibrin clots supports fibrinolysis, tissue damage and inflammation. Despite the importance of integrins in neutrophil attachment to fibrin-coated surfaces under flow conditions, little is known about their role in migration processes in shear free two-dimensional (2D) and three-dimensional (3D) fibrin(ogen) environments. Therefore, the present study was designed to study the role of functional integrins in mediating neutrophil migration on and in fibrin matrices. Time lapse video sequences of neutrophil chemokinesis and chemotaxis were made under conditions of active- or non-active integrins. Interestingly, migration of neutrophils on 2D fibrinogen coated surfaces and 3D fibrin matrices is independent of integrins as the response is not sensitive to αM-(CD11b) and β2-(CD18) blocking antibodies and/or chelation of Ca2+ and Mg2+ by EDTA in bivalent ion-free buffers. The blocking integrin antibodies were shown to be functionally active in regular adhesion assays. Our study shows that integrins are dispensable for migration on 2D and in 3D fibrin matrices, both when neutrophils enter into the fibrin matrix and when captured in the matrix.
BMS-593214, an active site-directed factor VIIa inhibitor: Enzyme kinetics, antithrombotic and antihaemostatic studies
Authors: Luettgen Joseph , Rendina Alan , Kettner Charles , Xin Baomin , Knabb Robert , Wexler Ruth , Priestley E. Scott , Wong Pancras
Published: June 2010

Factor (F) VIIa in association with tissue factor (TF) is the primary in vivo initiator of blood coagulation and activates FX and FIX to generate thrombin, which plays a key role in the pathogenesis of thrombosis. We evaluated the enzyme kinetics, antithrombotic and antihaemostatic properties of BMS-593214, an active-site, direct FVIIa inhibitor. Studies were conducted in enzymatic assays, and in anesthetised rabbit models of electrically-induced carotid arterial thrombosis (AT), thread-induced vena cava venous thrombosis (VT) and cuticle bleeding time (BT). Antithrombotic efficacy of BMS-593214 given intravenously was evaluated for both the prevention and treatment of AT and VT. BMS-593214 displayed direct, competitive inhibition of human FVIIa in the hydrolysis of a tripeptide substrate with Ki of 5 nM. However, it acted as a noncompetitive inhibitor of the activation of the physiological substrate FX by TF/VIIa with Ki of 9.3 nM. BMS-593214 showed selectivity for FVIIa and exhibited species differences in TF-FVIIa-dependent anticoagulation with similar potency in human and rabbit plasma. BMS-593214 was efficacious in the prevention and treatment models of AT and VT with ED50 values of 1.1 to 3.1 mg/kg. Furthermore, BMS-593214 exhibited a wide therapeutic window with respect to BT. These results suggest that inhibition of FVIIa with small-molecule active-site inhibitors represents a promising antithrombotic approach for the development of new therapies for the prevention and treatment of AT and VT.
A randomised pilot trial of the anti-von Willebrand factor aptamer ARC1779 in patients with type 2b von Willebrand disease
Authors: Paulinska Petra , Jilma-Stohlawetz Petra , Gilbert James , Hutabarat Renta , Knöbl Paul , Jilma Bernd
Published: June 2010

Desmopressin aggravates thrombocytopenia in type 2B von Willebrand disease (VWF type 2B) by release of large and hyper-adhesive von Wille-brand Factor (VWF) multimers. This pilot study investigated whether the anti-VWF aptamer ARC1779 can prevent desmopressin-induced thrombocytopenia and interferes with the excessive VWF turnover in patients with VWF type 2B. Concentration effect curves of ARC1779 were established for five patients in vitro and two patients with VWF type 2B were treated by infusion of ARC1779, desmopressin, or their combination in a randomised, controlled, double-blind design. ARC1779 concentrations in the range of 1–3 μg/ml blocked free A1 domain binding sites by 90% in vitro. In vivo, desmopressin alone induced a profound (-90%) drop in platelet counts in one of the patients. ARC1779 (4–5 μg/ml) completely inhibited VWF A1 domains and prevented this desmopress-in-induced platelet drop. Desmopressin alone increased VWF antigen two- to three-fold, accompanied by concordant changes in VWF Ristocetin cofactor activity (RCo) and coagulation factor VIII activity. ARC1779 substantially enhanced the desmopressin-induced maximal increase in these parameters, and improved multimer patterns. No treatment related adverse events were observed and no bleeding occurred despite marked thrombocytopenia. These data provide first proof of concept in humans and evidence that ARC1779 is a potent inhibitor of VWF. ARC1779 prevented the rapid consumption of VWF multimers together with agglutinated platelets that occurred in response to desmopressin challenge in patients with VWD type 2B.

Clinical Trial registration number: NCT00632242.
Reconstruction of Global Monthly Upper-Level Temperature and Geopotential Height Fields Back to 1880
Authors: Griesser Thomas , Brönnimann Stefan , Grant Andrea , Ewen Tracy , Stickler Alexander , Comeaux Joey
Published: June 2010

This work presents statistically reconstructed global monthly mean fields of temperature and geopotential height (GPH) up to 100 hPa for the period 1880–1957. For the statistical model several thousand predictors were used, comprising a large amount of historical upper-air data as well as data from the earth’s surface. In the calibration period (1958–2001), the statistical models were fit using the 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) as the predictand. After the weighting of the predictors, principal component (PC) analyses were performed on both the predictand and predictor dataset. Multiple linear regression models relate each principal component time series from the predictand with an optimal subset of principal component time series from the predictor. To assess the quality of the reconstructions, statistical split-sample validation (SSV) experiments were performed within the calibration period. Furthermore, the reconstructions were compared with independent historical upper-air and total ozone data. Based on the SSV experiment, this study obtained good reconstructions for temperature and GPH in the Northern Hemisphere; however, the skill in the tropics and the Southern Hemisphere was much lower. The reconstruction skill shows a clear annual cycle with the highest values in January. The lower levels were better reconstructed except in the tropics where the highest levels showed the best skill. With the inclusion of a considerable amount of upper-air data after 1939 the skill increased substantially. The fields were analyzed for selected months in the 1920s and 1930s to demonstrate the usefulness of the reconstructions. It is shown that the reconstructions are able to capture regional-to-global dynamical features.
Regional Climate Model Projections and Uncertainties of U.S. Summer Heat Waves
Authors: Kunkel Kenneth E. , Liang Xin-Zhong , Zhu Jinhong
Published: June 2010

Regional climate model (RCM) simulations, driven by low and high climate-sensitivity coupled general circulation models (CGCMs) under various future emissions scenarios, were compared to projected changes in heat wave characteristics. The RCM downscaling reduces the CGCM biases in heat wave threshold temperature by a factor of 2, suggesting a higher credibility in the future projections. All of the RCM simulations suggest that there is a high probability of heat waves of unprecedented severity by the end of the twenty-first century if a high emissions path is followed. In particular, the annual 3-day heat wave temperature increases generally by 3°–8°C; the number of heat wave days increases by 30–60 day yr−1 over much of the western and southern United States with slightly smaller increases elsewhere; the variance spectra for intermediate, 3–7 days (prolonged, 7–14 days), temperature extremes increase (decrease) in the central (western) United States. If a lower emissions path is followed, then the outcomes range from quite small changes to substantial increases. In all cases, the mean temperature climatological shift is the dominant change in heat wave characteristics, suggesting that adaptation and acclimatization could reduce effects.
A Dynamical Index for the East Asian Winter Monsoon
Authors: Li Yueqing , Yang Song
Published: June 2010

A new index measuring the East Asian winter monsoon is defined using the mean wind shears of upper-tropospheric zonal wind based on the belief that the physical processes of both higher and lower latitudes, and at both lower and upper troposphere, should be considered to depict the variability of monsoon. When the index is high (low), the westerly jet is strong (weak), the East Asian trough is deep (shallow), the Siberian high is strong (weak), and anomalous low-level northerlies (southerlies) prevail over East Asia. As a result, the surface and lower-tropospheric temperature over East Asia decreases (increases) and the cold surges over Southeast Asia and tropical western Pacific are more (less) active. The index, which exhibits distinct interannual variations, is also strongly correlated with the Arctic Oscillation and Niño-3.4 sea surface temperature (SST) index. Compared to previous indexes, this index takes into account more influencing factors and better elucidates the physical processes associated with monsoon, enhancing interpretations of the variability of monsoon and its effects on regional weather and climate. Furthermore, the monsoon index is significantly linked to antecedent tropical Pacific SST and is highly predictable in the NCEP Climate Forecast System, indicating the advantage of the index for operational predictions of monsoon.
Annual Volume and Area Variations in Tropical Cyclone Rainfall over the Eastern United States
Authors: Nogueira Ricardo C. , Keim Barry D.
Published: June 2010

This paper examines tropical cyclone (TC) rainfall in the eastern United States from the perspective of documenting accumulated annual water volumes and areas of the precipitation. Volume is a value that merges both rainfall depth and rainfall area into a single metric for each year that can be directly compared between individual years. Area represents the total land area affected by tropical rains. These TC rainfall metrics were then compared to the ENSO and the Atlantic multidecadal oscillation (AMO). Time series of annual TC water volumes show an annual average of 107 km3. The maximum volume was produced in 1985 with 405.8 km3, driven by Hurricanes Bob, Claudette, Danny, Elena, Gloria, Henri, Juan, and Kate as well as by Tropical Storms Henri and Isabel. The lowest TC volume occurred in 1978 with 8.9 km3. ENSO phases did not show any statistical correlation with TC frequency in the eastern United States. However, AMO showed a significant correlation with volume and the number of storms affecting the region. TC rainfall volume and area in the eastern United States showed a strong correlation. However, there are exceptions, whereby 1985 stands out as an exceptional volume year though the area affected is not as impressive. In contrast, 1979 is an example when TCs covered a large area with a corresponding small rainfall volume, in part because of the rapid forward movement of the storms, for example, Hurricanes David and Frederic. Since 1995, TCs have become more numerous, producing larger volumes and affecting larger areas.
Surface Layer Heat Balance in the Eastern Equatorial Pacific Ocean on Interannual Time Scales: Influence of Local versus Remote Wind Forcing*
Authors: Zhang Xuebin , McPhaden Michael J.
Published: June 2010

The authors use a new and novel heat balance formalism for the upper 50 m of the Niño-3 region (5°N–5°S, 90°–150°W) to investigate the oceanographic processes underlying interannual sea surface temperature (SST) variations in the eastern equatorial Pacific. The focus is on a better understanding of the relationship between local and remote atmospheric forcing in generating SST anomalies associated with El Niño–Southern Oscillation (ENSO) events. The heat balance analysis indicates that heat advection across 50-m depth and across 150°W are the important oceanic mechanisms responsible for temperature variations with the former being dominant. On the other hand, net surface heat flux adjusted for penetrative radiation damps SST. Jointly, these processes can explain most of interannual variations in temperature tendency averaged over the Niño-3 region. Decomposition of vertical advection across the bottom indicates that the mean seasonal advection of anomalous temperature (the so-called thermocline feedback) dominates and is highly correlated with 20°C isotherm depth variations, which are mainly forced by remote winds in the western and central equatorial Pacific. Temperature advection by anomalous vertical velocity (the “Ekman feedback”), which is highly correlated with local zonal wind stress variations, is smaller with an amplitude of about 40% on average of remotely forced vertical heat advection. These results support those of recent empirical and modeling studies in which local atmospheric forcing, while not dominant, significantly affects ENSO SST variations in the eastern equatorial Pacific.
Observational Evaluation of a Convective Quasi-Equilibrium View of Monsoons
Authors: Nie Ji , Boos William R. , Kuang Zhiming
Published: June 2010

Idealized dynamical theories that employ a convective quasi-equilibrium (QE) treatment for the diabatic effects of moist convection have been used to explain the location, intensity, and intraseasonal evolution of monsoons. This paper examines whether observations of the earth’s regional monsoons are consistent with the assumption of QE. It is shown here that in local summer climatologies based on reanalysis data, maxima of free-tropospheric temperature are, indeed, nearly collocated with maxima of subcloud equivalent potential temperature, θeb, in all monsoon regions except the North and South American monsoons. Free-tropospheric temperatures over North Africa also exhibit a strong remote influence from the South Asian monsoon. Consistent with idealized dynamical theories, peak precipitation falls slightly equatorward of the maxima in θeb and free-tropospheric temperature in regions where QE seems to hold.

Vertical structures of temperature and wind reveal two types of monsoon circulations. One is the deep, moist baroclinic circulation clearly seen in the South Asian monsoon. The other is of mixed type, with the deep moist circulation superimposed on a shallow dry circulation closely associated with boundary layer temperature gradients. While the existence of a shallow dry circulation has been documented extensively in the North African monsoon, here it is shown to also exist in Australia and southern Africa during the local summer. Analogous to moist QE theories for the deep circulation, the shallow circulation can be viewed in a dry QE framework in which shallow ascent occurs just equatorward of the peak boundary layer potential temperature, θb, providing a unified system where the poleward extents of deep and shallow circulations are bounded by maxima in θeb and θb, respectively.
Variations in the Flow of the Global Atmosphere Associated with a Composite Convectively Coupled Oceanic Kelvin Wave
Authors: Roundy Paul E. , Gribble-Verhagen Lynn M.
Published: June 2010

Kelvin waves in the Pacific Ocean occasionally develop and propagate eastward together with anomalies of deep convection and low-level westerly wind. This pattern suggests coupling between the oceanic waves and atmospheric convection. A simple composite analysis based on observed coupled events from October through April demonstrates that this apparent coupled mode is associated with significant large anomalies in the global flow that extend to high latitudes. These high-latitude anomalies are significantly larger than those that are linearly associated with the El Niño–Southern Oscillation (ENSO), and they evolve on time scales between those of the Madden–Julian oscillation and ENSO, potentially providing an opportunity for enhanced subseasonal predictability in the flow of the global atmosphere.
Note-Taking Skills of Middle School Students With and Without Learning Disabilities
Authors: Boyle Joseph R.
Published: June 2010

For middle school students with learning disabilities (LD), one major component of learning in content area classes, such as science, involves listening to lectures and recording notes. Lecture learning and note-taking are critical skills for students to succeed in these classes. Despite the importance of note-taking skills, no research has been reported on the problems that school-age students with LD encounter when recording notes during science lectures. Using a sample size of 90 middle school students, the performance of students with LD was compared to students with no learning disabilities (NLD). Results found that students with LD performed significantly worse than students with NLD in terms of the type and amount of notes recorded and test performance.
Canine Gastric Carcinoma
Authors: Carrasco V. , Canfrán S. , Rodríguez-Franco F. , Benito A. , Sáinz A. , Rodríguez-Bertos A.
Published: June 2010

Immunohistochemical staining for cell cycle proteins and heat shock proteins was performed on 17 canine gastric carcinomas. The immunoexpression of p53, p21, p16, Hsp27, and Hsp70 was investigated. A study was conducted to determine the histological type and parameters related to tumor malignancy. Possible associations and trends were assessed between the immunoexpression of each protein and tumor type as well as specific parameters of malignancy. High intratumor frequency of cellular p53 immunostaining was observed (61.96% average), but lower frequencies of p21 and p16 expression were present (34.65% and 10.41%, respectively). The p53 overexpression was associated with tumor infiltration ( P = .0258). Expression of p21 was lower in undifferentiated carcinomas, and the loss of expression was associated with histopathological parameters characteristic of a poor prognosis such as lymphatic vessel invasion ( P = .0258). The lack of p16 immunoreactivity was related to histopathological characteristics of malignancy such as the presence of evident and multiple nucleoli ( P = .0475). In contrast, deep tumor infiltration was observed in those carcinomas with a high p16 index ( P = .0475). Hsp70 appeared to be overexpressed in all gastric neoplasms included in this study. This is in contrast to Hsp27, because a group of tumors showed complete lack of Hsp27 immunoexpression, whereas the others displayed extensive Hsp27 immunostaining. The differences in Hsp27 did not correlate with any of the histopathological parameters, but Hsp27 immunoexpression was higher in the undifferentiated carcinoma. No significant differences in the expression of the proteins were found in canine gastric carcinomas according to their histological type. These findings may be useful for establishing a prognosis for canine gastric carcinoma.
Dating Violence and Substance Use Among Ethnically Diverse Adolescents
Authors: Temple Jeff R. , Freeman Daniel H.
Published: June 2010

Teen dating violence is a serious public health concern with numerous and long-lasting consequences. Although alcohol and drug use have been associated with dating violence, little is known about the role of specific substances, especially the use of club drugs and the nonmedical use of prescription drugs. Thus, the authors examined the association between dating violence victimization and the use of a variety of licit and illicit substances among 1,565 ethnically diverse and economically disadvantaged high school students in southeast Texas. Past year dating violence victimization was reported by 14.1% of boys and 11.3% of girls. Compared to their nonabused counterparts, youth who experienced dating violence were more likely to smoke cigarettes, drink alcohol, binge drink alcohol, sniff glue to get high, use marijuana, use ecstasy, use Vicodin, and use Xanax. However, with the exception of alcohol and cigarettes, all substances were reduced to nonsignificance in multivariate analyses. No differences were found in the rate of dating violence between African American, White, and Hispanic adolescents.
Psychometric Properties of an Intimate Partner Violence Tool for Health Care Students
Authors: Connor Pamela D. , Nouer Simonne S. , Mackey Seé Trail N. , Tipton Nathan G. , Lloyd Angela K.
Published: June 2010

Health care professionals have acknowledged intimate partner violence (IPV) as a highly prevalent public health problem necessitating the creation of standardized education programs, survey tools, and well-defined outcome measures. Testing and evaluation of these measures, however, has been limited to specific populations of health care professionals. In 2007 and 2008, psychometric properties of the Physician Readiness to Manage Intimate Partner Violence Survey (PREMIS) were adapted, tested, and evaluated on a group of medicine, nursing, social work, and dentistry students during their last semester of college. The adapted instrument demonstrated high reliability within some IPV constructs, and six of the eight scales described in the original PREMIS were identified. Three scales presented a Cronbach’s α ≥ .70, demonstrating acceptable reliability, and a new scale, IPV Screening, was also identified that showed good reliability (α = .74). The adapted instrument showed good stability of psychometric properties in the student population and generally good correlation within several measures.
Male Social Workers Working With Men Who Batter: Dilemmas in Gender Identity
Authors: Bailey Benjamin , Buchbinder Eli , Eisikovits Zvi
Published: June 2010

Research into the impact of dealing with intimate partner violence has focused mainly on women who treated victims. The present article explores the interaction between male social workers and battering men. The sample included 15 male social workers who worked with battering men in social services. Data collection was performed through semistructured interviews. The main theme emerging from the interviews describes the reconstruction and renegotiation of the worker’s professional and personal self in light of his experiences with violent clients. Two major motifs describing their experience emerged: The first is self-doubt arising from adopting a broad definition of violence, thus creating increased sensitization to and inclusion of a wide range of behaviors under the term violence . The second motif is related to compromising with reality by renegotiating their identity as aggressive, at times, but not violent. Findings were discussed in the light of the constructionist perspective.
Mexican Americans With Type 2 Diabetes in an Emerging Latino Community: Evaluation of Health Disparity Factors and Interventions
Authors: Amirehsani Karen A.
Published: June 2010

Mexican Americans suffer from disproportionately higher rates of type 2 diabetes and its associated complications than the general population. They also confront significant obstacles to health care access and may not receive the same quality of health care as non-Hispanic Whites. Understanding the factors contributing to their health disparities is critical for nurses and other health care providers working with Latino immigrants, especially those in emerging Latino communities such as North Carolina who may lack the established infrastructure of more traditional Latino communities. The purpose of this article is to explicate these factors and examine culturally competent diabetes interventions being used to assist Mexican Americans increase their knowledge of diabetes and health promoting behaviors in order to achieve better glycemic control and prevent complications.
How Parents Perceive and Feel about Participation in Community Activities
Authors: Lam Shui-Fong , Wong Bernard P.H. , Leung Doris , Ho Daphne , Au-Yeung Peter
Published: June 2010

The present study compared how parents of preschoolers with and without Autism Spectrum Disorders (ASD) perceived and felt about participation in community activities. A questionnaire survey was conducted with 380 Hong Kong parents of preschoolers with ASD and 214 Hong Kong parents of preschoolers without ASD. The two groups were not different in their willingness and frequency of participation in community activities. However, the psychological processes underneath their willingness were very different. Among the parents of preschoolers with ASD, their willingness was associated with how they perceived the difficulty and importance of the participation and what emotions they experienced during the activities. This pattern of association was not evident among the parents of preschoolers without ASD.
Nostalgia, coming home, and the end of the poem: On reading William Wordsworth’s Ode. Intimations of Immortality from Recollections of Early Childhood
Authors: Abbott Ruth
Published: June 2010

Reconsidering the functions of nostalgia during the reading of poems, this article argues that nostalgic longing may be a more creative and critical force than we often think it. As both are understood in our century, nostalgia can seem antithetical to critical reading. But time passes during reading, as well as between readings: the very shape of reading, processing from beginning to inevitable end, means something is always being left behind - something of which a poem’s marking of time through rhythm makes us particularly aware. Reading one almost definitively nostalgic poem by an equally definitively nostalgic poet - William Wordsworth’s Ode. Intimations of Immortality from Recollections of Early Childhood - the article explores what happens between the moment when a poem begins to speak and the moment it falls into silence. Focusing on some of the ways in which time is experienced while a poem is read, it argues for nostalgia as integral rather than detrimental to reading, with particular functions in relation to poetry worth our reconsideration.
The agency of yearning on the Northwest Coast of Canada: Franz Boas, George Hunt and the salvage of autochthonous culture
Authors: Whitehead Harry
Published: June 2010

In this article, I consider the ethnographic research undertaken by the anthropologist, Franz Boas, and his researcher, George Hunt, among the Kwakwaka’wakw people of British Columbia, Canada, in the late 19th and early 20th centuries. I show some of the ways in which the Kwakwaka’wakw use that material today. In doing this, I argue for the positive agency of nostalgia in practice for minority groups such as the Kwakwaka’wakw.
An in vivo model of double-unit cord blood transplantation that correlates with clinical engraftment
Authors: Eldjerou Lamis K. , Chaudhury Sonali , Baisre-de Leon Ada , He Mai , Arcila Maria E. , Heller Glenn , O'Reilly Richard J. , Barker Juliet N. , Moore Malcolm A.
Published: June 2010

Double-unit cord blood transplantation (DCBT) appears to enhance engraftment despite sustained hematopoiesis usually being derived from a single unit. To investigate DCBT biology, in vitro and murine models were established using cells from 39 patient grafts. Mononuclear cells (MNCs) and CD34+ cells from each unit alone and in DCB combination were assessed for colony-forming cell and cobblestone area-forming cell potential, and multilineage engraftment in NOD/SCID/IL2R-γnull mice. In DCB assays, the contribution of each unit was measured by quantitative short tandem repeat region analysis. There was no correlation between colony-forming cell (n = 10) or cobblestone area-forming cell (n = 9) numbers and clinical engraftment, and both units contributed to DCB cocultures. In MNC transplantations in NOD/SCID/IL2R-γnull mice, each unit engrafted alone, but MNC DCBT demonstrated single-unit dominance that correlated with clinical engraftment in 18 of 21 cases (86%, P < .001). In contrast, unit dominance and clinical correlation were lost with CD34+ DCBT (n = 11). However, add-back of CD34− to CD34+ cells (n = 20) restored single-unit dominance with the dominant unit correlating not with clinical engraftment but also with the origin of the CD34− cells in all experiments. Thus, unit dominance is an in vivo phenomenon probably associated with a graft-versus-graft immune interaction mediated by CD34− cells.
Impact of in vivo alemtuzumab dose before reduced intensity conditioning and HLA-identical sibling stem cell transplantation: pharmacokinetics, GVHD, and immune reconstitution
Authors: Chakraverty Ronjon , Orti Guillermo , Roughton Michael , Shen Jun , Fielding Adele , Kottaridis Panagiotis , Milligan Donald , Collin Matthew , Crawley Charles , Johnson Peter , Clark Andrew , Parker Anne , Bloor Adrian , Pettengell Ruth , Snowden John , Pettitt Andrew , Clark Richard , Hale Geoff , Peggs Karl , Thomson Kirsty , Morris Emma , Mackinnon Stephen
Published: June 2010

In vivo alemtuzumab reduces the risk of graft-versus-host disease (GVHD) and nonrelapse mortality after reduced intensity allogeneic transplantation. However, it also delays immune reconstitution, leading to frequent infections and potential loss of graft-versus-tumor responses. Here, we tested the feasibility of alemtuzumab dose deescalation in the context of fludarabine-melphalan conditioning and human leukocyte antigen (HLA)–identical sibling transplantation. Alemtuzumab was given 1-2 days before graft infusion, and dose reduced from 60 mg to 20 mg in 4 sequential cohorts (total n = 106). Pharmacokinetic studies were fitted to a linear, 2-compartment model in which dose reduction led to incomplete saturation of CD52 binding sites and greater antibody clearance. Increased elimination was particularly evident in the 20-mg group in patients who had CD52-expressing tumors at time of transplantation. The 20-mg dose was also associated with greater risk of severe GVHD (acute grade III-IV or chronic extensive) compared with > 20 mg (hazard ratio, 6.7; 95% CI, 2.5-18.3). In contrast, dose reduction to 30 mg on day −1 was associated with equivalent clinical outcomes to higher doses but better lymphocyte recovery at 12 months. In conclusion, alemtuzumab dose reduction to 30 mg is safe in the context of reduced intensity conditioning and HLA-identical sibling transplantation. This trial was registered at http://www.ncrn.org.uk as UKCRN study 1415.
Neoplastic transformation of breast epithelial cells by genotoxic stress
Authors: Botlagunta Mahendran , Winnard Paul T , Raman Venu
Published: June 2010

Background

Exposure to genotoxic stresses such as radiation and tobacco smoke can cause increased cancer incidence rate as reflected in an in depth meta-analysis of data for women and breast cancer incidence. Published reports have indicated that exposures to low dose radiation and tobacco smoke are factors that contribute to the development of breast cancer. However, there is a scarcity of information on the combinatorial effects of low dose radiation and tobacco smoke on formation and progression of breast cancer. The combination of these two genotoxic insults can induce significant damage to the genetic material of the cells resulting in neoplastic transformation.

Methods

To study the effects of low dose ionizing radiation and tobacco smoke on breast cells, MCF 10A cells were treated either with radiation (Rad - 0.1 Gray) or cigarette smoke condensate (Csc - 10 microgram/ml of medium) or a combination of Rad + Csc. Following treatments, cells were analyzed for cell cycle distribution patterns and the ability to extrude the Hoechst 33342 dye. In addition, in vitro invasion and migration as well as mammosphere formation assays were performed. Finally, differential gene expression profiles were generated from the individual and combination treatment.

Results

Exposure of MCF 10A cells to the combination of radiation plus cigarette smoke condensate generated a neoplastic phenotype. The transformed phenotype promoted increased mammosphere numbers, altered cell cycle phases with a doubling of the population in S phase, and increased invasion and motility. Also, exclusion of Hoechst 33342 dye, a surrogate marker for increased ABC transporters, was observed, which indicates a possible increase in drug resistance. In addition, changes in gene expression include the up regulation of genes encoding proteins involved in metabolic pathways and inflammation.

Conclusions

The results indicate that when normal breast cells are exposed to low dose radiation in combination with cigarette smoke condensate a phenotype is generated that exhibits traits indicative of neoplastic transformation. More importantly, this is the first study to provide a new insight into a possible etiology for breast cancer formation in individuals exposed to low dose radiation and tobacco smoke.
Clinical impact of bladder biopsies with TUR-BT according to cytology results in patients with bladder cancer: a case control study
Authors: Matsushima Masashi , Kikuchi Eiji , Hasegawa Masanori , Matsumoto Kazuhiro , Miyajima Akira , Oya Mototsugu
Published: June 2010

Background

There seems to be no consensus concerning taking bladder biopsies during transurethral resection of bladder tumor (TUR-BT). We investigate the clinical significance of bladder biopsy with TUR-BT and the relationship between urinary cytology and the biopsy results.

Methods

We reviewed a total of 424 patients with non-muscle invasive bladder cancer treated with TUR-BT between 1998 and 2005. Of the total, 293 patients also underwent a bladder biopsy. Biopsies from suspicious-appearing urothelium (N = 59) and those from normal-appearing urothelium (N = 234) were evaluated separately.

Results

Bladder cancer was observed in 23 cases (39.0%) who underwent a biopsy of suspicious-appearing urothelium. Among these 23 cases, 9 cases with visible tumor resection had carcinoma in situ (CIS) only in the biopsies from suspicious-appearing urothelium. Urinary cytology was negative in 3 of the 9 cases. Bladder cancer was observed in 26 cases (11.1%) who underwent a biopsy of normal-appearing urothelium. Of them, 5 cases with visible tumors had CIS only in the multiple biopsies from normal-appearing urothelium. Urinary cytology was positive in all of the 5 cases. No upstaging or upgrading cases were found in these patients by the addition of these two types of biopsy. Furthermore, therapy was not altered in these patients. With or without bladder biopsy was not a significant factor for tumor recurrence in either the univariate or multivariate analysis.

Conclusions

Based on the results, it is concluded the multiple biopsies from normal-appearing urothelium are not necessary in patients with negative cytology results because of the low detection rate and lack of influence on therapeutic decisions. Meanwhile, biopsy of suspicious-appearing urothelium is needed in patients with negative cytology results in order to detect CIS due to staging properties. This result supports a recent EAU guideline.
Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan
Authors: Teede H , Deeks A , Moran L
Published: June 2010

Polycystic ovary syndrome (PCOS) is of clinical and public health importance as it is very common, affecting up to one in five women of reproductive age. It has significant and diverse clinical implications including reproductive (infertility, hyperandrogenism, hirsutism), metabolic (insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, adverse cardiovascular risk profiles) and psychological features (increased anxiety, depression and worsened quality of life). Polycystic ovary syndrome is a heterogeneous condition and, as such, clinical and research agendas are broad and involve many disciplines. The phenotype varies widely depending on life stage, genotype, ethnicity and environmental factors including lifestyle and bodyweight. Importantly, PCOS has unique interactions with the ever increasing obesity prevalence worldwide as obesity-induced insulin resistance significantly exacerbates all the features of PCOS. Furthermore, it has clinical implications across the lifespan and is relevant to related family members with an increased risk for metabolic conditions reported in first-degree relatives. Therapy should focus on both the short and long-term reproductive, metabolic and psychological features. Given the aetiological role of insulin resistance and the impact of obesity on both hyperinsulinaemia and hyperandrogenism, multidisciplinary lifestyle improvement aimed at normalising insulin resistance, improving androgen status and aiding weight management is recognised as a crucial initial treatment strategy. Modest weight loss of 5% to 10% of initial body weight has been demonstrated to improve many of the features of PCOS. Management should focus on support, education, addressing psychological factors and strongly emphasising healthy lifestyle with targeted medical therapy as required. Monitoring and management of long-term metabolic complications is also an important part of routine clinical care. Comprehensive evidence-based guidelines are needed to aid early diagnosis, appropriate investigation, regular screening and treatment of this common condition. Whilst reproductive features of PCOS are well recognised and are covered here, this review focuses primarily on the less appreciated cardiometabolic and psychological features of PCOS.
Presence of a classical RRM-fold palm domain in Thg1-type 3'- 5'nucleic acid polymerases and the origin of the GGDEF and CRISPR polymerase domains
Authors: Anantharaman Vivek , Iyer Lakshminarayan M , Aravind L
Published: June 2010

Background

Almost all known nucleic acid polymerases catalyze 5'-3' polymerization by mediating the attack on an incoming nucleotide 5' triphosphate by the 3'OH from the growing polynucleotide chain in a template dependent or independent manner. The only known exception to this rule is the Thg1 RNA polymerase that catalyzes 3'-5' polymerization in vitro and also in vivo as a part of the maturation process of histidinyl tRNA. While the initial reaction catalyzed by Thg1 has been compared to adenylation catalyzed by the aminoacyl tRNA synthetases, the evolutionary relationships of Thg1 and the actual nature of the polymerase reaction catalyzed by it remain unclear.

Results

Using sensitive profile-profile comparison and structure prediction methods we show that the catalytic domain Thg1 contains a RRM (ferredoxin) fold palm domain, just like the viral RNA-dependent RNA polymerases, reverse transcriptases, family A and B DNA polymerases, adenylyl cyclases, diguanylate cyclases (GGDEF domain) and the predicted polymerase of the CRISPR system. We show just as in these polymerases, Thg1 possesses an active site with three acidic residues that chelate Mg++ cations. Based on this we predict that Thg1 catalyzes polymerization similarly to the 5'-3' polymerases, but uses the incoming 3' OH to attack the 5' triphosphate generated at the end of the elongating polynucleotide. In addition we identify a distinct set of residues unique to Thg1 that we predict as comprising a second active site, which catalyzes the initial adenylation reaction to prime 3'-5' polymerization. Based on contextual information from conserved gene neighborhoods we show that Thg1 might function in conjunction with a polynucleotide kinase that generates an initial 5' phosphate substrate for it at the end of a RNA molecule. In addition to histidinyl tRNA maturation, Thg1 might have other RNA repair roles in representatives from all the three superkingdoms of life as well as certain large DNA viruses. We also present evidence that among the polymerase-like domains Thg1 is most closely related to the catalytic domains of the GGDEF and CRISPR polymerase proteins.

Conclusion

Based on this relationship and the phyletic patterns of these enzymes we infer that the Thg1 protein is likely to represent an archaeo-eukaryotic branch of the same clade of proteins that gave rise to the mobile CRISPR polymerases and in bacteria spawned the GGDEF domains. Thg1 is likely to be close to the ancestral version of this family of enzymes that might have played a role in RNA repair in the last universal common ancestor.

Reviewers

This article was reviewed by S. Balaji and V.V. Dolja.
Malignant mammary tumor in female dogs: environmental contaminants
Authors: Andrade Fábio HE , Figueiroa Fernanda C , Bersano Paulo RO , Bissacot Denise Z , Rocha Noeme S
Published: June 2010

Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits.