bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of hTERT by BCR-ABL at multiple levels in K562 cells
Authors: Chai Juin Hsien , Zhang Yong , Tan Wei Han , Chng Wee Joo , Li Baojie , Wang Xueying 
Published: December 2011

Abstract

Background
The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that BCR-ABL is the specific target of Gleevec in CML treatment, we investigated the regulation of the catalytic component of telomerase, hTERT, by BCR-ABL at multiple levels in K562 cells.

Methods
Molecular techniques such as over expression, knockdown, real-time PCR, immunoprecipitation, western blotting, reporter assay, confocal microscopy, telomerase assays and microarray were used to suggest that hTERT expression and activity is modulated by BCR-ABL at multiple levels.

Results
Our results suggest that BCR-ABL plays an important role in regulating hTERT in K562 (BCR-ABL positive human leukemia) cells. When Gleevec inhibited the tyrosine kinase activity of BCR-ABL, phosphorylation of hTERT was downregulated, therefore suggesting a positive correlation between BCR-ABL and hTERT. Gleevec treatment inhibited hTERT at mRNA level and significantly reduced telomerase activity (TA) in K562 cells, but not in HL60 or Jurkat cells (BCR-ABL negative cells). We also demonstrated that the transcription factor STAT5a plays a critical role in hTERT gene regulation in K562 cells. Knockdown of STAT5a, but not STAT5b, resulted in a marked downregulation of hTERT mRNA level, TA and hTERT protein level in K562 cells. Furthermore, translocation of hTERT from nucleoli to nucleoplasm was observed in K562 cells induced by Gleevec.

Conclusions
Our data reveal that BCR-ABL can regulate TA at multiple levels, including transcription, post-translational level, and proper localization. Thus, suppression of cell growth and induction of apoptosis by Gleevec treatment may be partially due to TA inhibition. Additionally, we have identified STAT5a as critical mediator of the hTERT gene expression in BCR-ABL positive CML cells, suggesting that targeting STAT5a may be a promising therapeutic strategy for BCR-ABL positive CML patients.
Plasma secretory phospholipase A2-IIa as a potential biomarker for lung cancer in patients with solitary pulmonary nodules
Authors: Kupert Elena , Anderson Marshall , Liu Yin , Succop Paul , Levin Linda , Wang Jiang , Wikenheiser-brokamp Kathryn , Chen Pingping , Pinney Susan M , Macdonald Trudy , Dong Zhongyun , Starnes Sandra , Lu Shan 
Published: December 2011

Abstract

Background
Five-year survival for lung cancer has remained at 16% over last several decades largely due to the fact that over 50% of patients are diagnosed with locally-advanced or metastatic disease. Diagnosis at an earlier and potentially curable stage is crucial. Solitary pulmonary nodules (SPNs) are common, but the difficulty lies in the determination of which SPN is malignant. Currently, there is no convenient and reliable biomarker effective for early diagnosis. Secretory phospholipase A2-IIa (sPLA2-IIa) is secreted into the circulation by cancer cells and may allow for an early detection of lung cancer.

Methods
Plasma samples from healthy donors, patients with only benign SPN, and patients with lung cancer were analyzed. Expression of sPLA2-IIa protein in lung cancer tissues was also determined.

Results
We found that the levels of plasma sPLA2-IIa were significantly elevated in lung cancer patients. The receiver operating characteristic curve analysis, comparing lung cancer patients to patients with benign nodules, revealed an optimum cutoff value for plasma sPLA2-IIa of 2.4 ng/ml to predict an early stage cancer with 48% sensitivity and 86% specificity and up to 67% sensitivity for T2 stage lung cancer. Combined sPLA2-IIa, CEA, and Cyfra21.1 tests increased the sensitivity for lung cancer prediction. High level of plasma sPLA2-IIa was associated with a decreased overall cancer survival. sPLA2-IIa was overexpressed in almost all non-small cell lung cancer and in the majority of small cell lung cancer by immunohistochemistry analysis.

Conclusion
Our finding strongly suggests that plasma sPLA2-IIa is a potential lung biomarker to distinguish benign nodules from lung cancer and to aid lung cancer diagnosis in patients with SPNs.
Evaluation of immunity against malaria using luciferase-expressing Plasmodium berghei parasites
Authors: Ploemen Ivo , Behet Marije , Nganou-Makamdop Krystelle , van Gemert Geert-Jan , Bijker Else , Hermsen Cornelus , Sauerwein Robert 
Published: December 2011

Abstract

Background
Measurement of liver stage development is of key interest in malaria biology and vaccine studies. Parasite development in liver cells can be visualized in real-time, both in culture and in live mice, using a transgenic Plasmodium berghei parasite, Pb GFP-Luccon, expressing the bioluminescent reporter luciferase. This study explores the benefit of using these parasites for the evaluation of immunity against malaria, compared to qRT-PCR techniques in vivo and in vitro.

Methods
Mice were immunized with either radiation attenuated sporozoites (RAS) or wildtype sporozoites under chloroquine prophylaxis (CPS) and challenged with Pb GFP-Luccon. The in vitro transgenic sporozoites neutralization assay (TSNA) was adapted by replacing Pb CS(Pf) parasites for Pb GFP-Luccon parasites.

Results
Application of Pb GFP-Luccon transgenic parasites provides live quantitative visual information about the relation between parasite liver load and protection. Moreover, fast and reproducible results are obtained by using these parasites in the transgenic sporozoites neutralization assay, measuring functional antibody-mediated immune responses.

Conclusions

Pb GFP-Luccon parasites are a straightforward and valuable tool for comprehension of the biological and immunological principles underlying protection against malaria.
Isolation and characterization of human spermatogonial stem cells
Authors: Liu Shixue , Tang Ziwei , Xiong Tao , Tang Wei 
Published: December 2011

Abstract

Background
To isolate and characterization of human spermatogonial stem cells from stem spermatogonium.

Methods
The disassociation of spermatogonial stem cells (SSCs) were performed using enzymatic digestion of type I collagenase and trypsin. The SSCs were isolated by using Percoll density gradient centrifugation, followed by differential surface-attachment method. Octamer-4(OCT4)-positive SSC cells were further identified using immunofluorescence staining and flow cytometry technques. The purity of the human SSCs was also determined, and a co-culture system for SSCs and Sertoli cells was established.

Results
The cell viability was 91.07% for the suspension of human spermatogonial stem cells dissociated using a two-step enzymatic digestion process. The cells isolated from Percoll density gradient coupled with differential surface-attachement purification were OCT4 positive, indicating the cells were human spermatogonial stem cells. The purity of isolated human spermatogonial stem cells was 86.7% as assessed by flow cytometry. The isolated SSCs were shown to form stable human spermatogonial stem cell colonies on the feeder layer of the Sertoli cells.

Conclusions
The two-step enzyme digestion (by type I collagenase and trypsin) process is an economical, simple and reproducible technique for isolating human spermatogonial stem cells. With little contamination and less cell damage, this method facilitates isolated human spermatogonial stem cells to form a stable cell colony on the supporting cell layer.
Adaptive selection of antenna grouping and beamforming for MIMO systems
Authors: Kim Kyungchul , Ko Kyungjun , Lee Jungwoo 
Published: December 2011

Abstract
Antenna grouping algorithms are hybrids of transmit beamforming and spatial multiplexing. With antenna grouping, we can achieve combining gain through transmit beamforming, and high spectral efficiency through spatial multiplexing. In an independent identically distributed channel, the antenna grouping method has better bit error rate (BER) performance than the beamforming method. However, if the channel is correlated, then the BER performance of antenna grouping degrades. In that case, it is better to use beamforming instead of antenna grouping. In this article, we investigate the mode selection algorithms which select between the antenna grouping and the beamforming modes. By selecting a suitable mode for a given channel, we can achieve more robustness of the system performance. We introduce several mode selection criteria as well as a low complexity criterion which is derived from a low complexity antenna grouping algorithm. Simulation results show that the proposed mode selection algorithm performs better than the antenna grouping and the beamforming modes in various channel conditions.
Non-Peptidergic Small Diameter Primary Afferents Expressing VGluT2 Project to Lamina I of Mouse Spinal Dorsal Horn
Authors: Clarke Jennifer N , Anderson Rebecca L , Haberberger Rainer V , Gibbins Ian L 
Published: December 2011

Background: Unmyelinated primary afferent nociceptors are commonly classified into two main functional types: those expressing neuropeptides, and non-peptidergic fibers that bind the lectin IB4. However, many small diameter primary afferent neurons neither contain any known neuropeptides nor bind IB4. Most express high levels of vesicular glutamate transporter 2 (VGluT2) and are assumed to be glutamatergic nociceptors but their terminations within the spinal cord are unknown. We used in vitro anterograde axonal tracing with Neurobiotin to identify the central projections of these putative glutamatergic nociceptors. We also quantitatively characterised the spatial arrangement of these terminals with respect to those that expressed the neuropeptide, calcitonin gene-related peptide (CGRP). Results: Neurobiotin-labeled VGluT2-immunoreactive (IR) terminals were restricted to lamina I, with a medial-tolateral distribution similar to CGRP-IR terminals. Most VGluT2-IR terminals in lateral lamina I were not labeled by Neurobiotin implying that they arose mainly from central neurons. 38 ± 4% of Neurobiotin-labeled VGluT2-IR terminals contained CGRP-IR. Conversely, only 17 ±4% of Neurobiotin-labeled CGRP-IR terminals expressed detectable VGluT2-IR. Neurobiotin-labeled VGluT2-IR or CGRP-IR terminals often aggregated into small clusters or microdomains partially surrounding intrinsic lamina I neurons. Conclusions: The central terminals of primary afferents which express high levels of VGluT2-IR but not CGRP-IR terminate mainly in lamina I. The spatial arrangement of VGluT2-IR and CGRP-IR terminals suggest that lamina I neurons receive convergent inputs from presumptive nociceptors that are primarily glutamatergic or peptidergic. This reveals a previously unrecognized level of organization in lamina I consistent with the presence of multiple nociceptive processing pathways.
Association between a single-pass whole-body computed tomography policy and survival after blunt major trauma: a retrospective cohort study
Authors: Hutter Martin , Woltmann Alexander , Hierholzer Christian , Gärtner Christian , Bühren Volker , Stengel Dirk 
Published: December 2011

Abstract

Introduction
Single-pass, whole-body computed tomography (pan-scan) remains a controversial intervention in the early assessment of patients with major trauma. We hypothesized that a liberal pan-scan policy is mainly an indicator of enhanced process quality of emergency care that may lead to improved survival regardless of the actual use of the method.

Methods
This retrospective cohort study included consecutive patients with blunt trauma referred to a trauma center prior to (2000 to 2002) and after (2002 to 2007) the introduction of a liberal single-pass pan-scan policy. The overall mortality between the two periods was compared and stratified according to the availability and actual use of the pan-scan. Logistic regression analysis was employed to adjust mortality estimates for demographic and injury-related independent variables.

Results
The study comprised 313 patients during the pre-pan-scan period, 223 patients after the introduction of the pan-scan policy but not undergoing a pan-scan and 608 patients undergoing a pan-scan. The overall mortality was 23.3, 14.8 and 7.9% (P < 0.001), respectively. By univariable logistic regression analysis, both the availability (odds ratio (OR) 0.57, 95% confidence interval (CI): 0.36 to 0.90) and the actual use of the pan-scan (OR 0.28, 95% CI: 0.19 to 0.42) were associated with a lower mortality. The final model contained the Injury Severity Score, the Glasgow Coma Scale, age, emergency department time and the use of the pan-scan. 2.7% of the explained variance in mortality was attributable to the use of the pan-scan. This contribution increased to 7.1% in the highest injury severity quartile.

Conclusions
In this study, a liberal pan-scan policy was associated with lower trauma mortality. The causal role of the pan-scan itself must be interpreted in the context of improved structural and process quality, is apparently moderate and needs further investigation with regard to the diagnostic yield and changes in management decisions. (The Pan-Scan for Trauma Resuscitation [PATRES] Study Group, ISRCTN35424832 and ISRCTN41462125)
Childhood maltreatment and the structure of common psychiatric disorders
Authors: Keyes Katherine M. , Eaton Nicholas R. , Krueger Robert F. , McLaughlin Katie A. , Wall Melanie M. , Grant Bridget F. , Hasin Deborah S. 
Published: December 2011

BackgroundPrevious research suggests that various types of childhood maltreatment frequently co-occur and confer risk for multiple psychiatric diagnoses. This non-specific pattern of risk may mean that childhood maltreatment increases vulnerability to numerous specific psychiatric disorders through diverse, specific mechanisms or that childhood maltreatment engenders a generalised liability to dimensions of psychopathology. Although these competing explanations have different implications for intervention, they have never been evaluated empirically.AimsWe used a latent variable approach to estimate the associations of childhood maltreatment with underlying dimensions of internalising and externalising psychopathology and with specific disorders after accounting for the latent dimensions. We also examined gender differences in these associations.MethodData were drawn from a nationally representative survey of 34 653 US adults. Lifetime DSM-IV psychiatric disorders were assessed using the AUDADIS-IV. Physical, sexual and emotional abuse and neglect were assessed using validated measures. Analyses controlled for other childhood adversities and sociodemographics.ResultsThe effects were fully mediated through the latent liability dimensions, with an impact on underlying liability levels to internalising and externalising psychopathology rather than specific psychiatric disorders. Important gender differences emerged with physical abuse associated only with externalising liability in men, and only with internalising liability in women. Neglect was not significantly associated with latent liability levels.ConclusionsThe association between childhood maltreatment and common psychiatric disorders operates through latent liabilities to experience internalising and externalising psychopathology, indicating that the prevention of maltreatment may have a wide range of benefits in reducing the prevalence of many common mental disorders. Different forms of abuse have gender-specific consequences for the expression of internalising and externalising psychopathology, suggesting gender-specific aetiological pathways between maltreatment and psychopathology.
Demise and Ascent
Authors: Holmes Todd 
Published: December 2011

This essay examines California Republican Senator Thomas Kuchel in honor of his 101 birthday this August, tracing Kuchel's fight against the conservative Right during the 1960s. More specifically, the essay highlights Kuchel as the last vestige of California's progressive Republicans and his effort to protect the GOP from right-wing corrosion and the likes of Nixon, Goldwater, George Murphy, and especially Ronald Reagan. Ultimately it was this effort that united the corporate conservatives of Reaganism to oust the 32 year political veteran in 1968.
Based on periodicals and primary research conducted in the political papers of Thomas Kuchel, Barry Goldwater, and Alan Cranston, the essay posits that remembering Kuchel will push us to reflect on the real change of the Republican Party under Reaganism, both nationally and in California. With no biographies written and his own centennial overshadowed by the political pageantry of Reagan's, remembering Thomas Kuchel offers an important and much needed political perspective.
Inverse Relationship between the Inflammatory Marker Pentraxin-3, Fat Body Mass, and Abdominal Obesity in End-Stage Renal Disease
Authors: Miyamoto Tetsu , Rashid Qureshi Abdul , Heimbürger Olof , Bárány Peter , Carrero Karin , Sjöberg Bodil , Lindholm Bengt , Stenvinkel Peter , Carrero Juan Jesús 
Published: December 2011

Summary

Background and objectives
Pentraxin-3 (PTX3) belongs to the same pentraxin superfamily of acute-phase reactants as C-reactive protein (CRP). Abdominal fat accumulation in ESRD is considered a chronic inflammatory state, but the relationship of PTX3 to this phenomenon is unknown. This study assesses plausible associations between PTX3 and surrogates of fat mass deposits in dialysis patients.

Design, setting, participants, & measurements
Circulating levels of PTX3, CRP, and IL-6 were cross-sectionally analyzed in relation to anthropometric and nutritional surrogate markers of fat tissue in two cohorts comprising 156 prevalent hemodialysis (HD) and 216 incident dialysis patients.

Results
In both cohorts, PTX3 was negatively associated with body mass index (BMI) and fat body mass index (FBMI) derived from anthropometrics and leptin, whereas there was a positive association with adiponectin. In prevalent HD patients, those with larger waist circumference (above gender-specific median values) had lower PTX3, higher CRP, and higher IL-6 levels. This was also true in multivariate analyses. In both cohorts, multivariate regression analyses showed that PTX3 was negatively and CRP (or IL-6) was positively associated with FBMI.

Conclusions
Although CRP and IL-6 were directly associated with body fat, PTX3 levels showed negative correlations with surrogates of adipose tissue in two independent cohorts of ESRD patients. Understanding the underlying reasons behind these opposite associations may have clinical relevance given the survival advantage described for obese patients on dialysis.
The Risk for Medial Arterial Calcification in CKD
Authors: Abou Hassan Nada , D’Orsi Ellen T. , D’Orsi Carl J. , O'Neill W. Charles 
Published: December 2011

Summary

Background and objectives
CKD is a risk factor for medial artery calcification, but the CKD stage at which this risk begins is unknown. Because breast arterial calcification (BAC) is a marker of generalized medial arterial calcification, mammography was used to detect medial arterial calcification in women with different CKD stages.

Design, setting, participants, & measurements
This was a retrospective, cross-sectional study of women with and without CKD matched for age and diabetes and identified from mammograms obtained in 2006–2011. BAC was scored as present or absent per visual inspection.

Results
A total of 146 women with stage 3 CKD and 54 with stage 4/5 CKD were identified. An additional 21 patients with ESRD were identified and added to a previous cohort of 71 patients. Mean age was 64 years for CKD 3, 63 for CKD 4, and 59 for ESRD. Half of each group had diabetes. Compared with controls, the odds ratios for BAC were 1.44 in CKD 3 (95% confidence interval [CI], 0.82–2.53), 2.69 in CKD 4 (95% CI, 1.14–6.33), and 7.19 in ESRD (95% CI, 3.77–13.7) and did not differ with diabetic status or race. In a multivariable logistic model, age (P<0.001) and estimated GFR (P=0.005) were independent predictors of BAC. The odds ratio for BAC increased 4% for each milliliter per minute per 1.73 m2 decrease in estimated GFR. The prevalence of BAC in CKD was increased in each decade of age over 49 years.

Conclusions
CKD is an independent risk factor for medial arterial calcification.
Dialysis Modality and Outcomes in Kidney Transplant Recipients
Authors: Molnar Miklos Z. , Mehrotra Rajnish , Duong Uyen , Bunnapradist Suphamai , Lukowsky Lilia R. , Krishnan Mahesh , Kovesdy Csaba P. , Kalantar-Zadeh Kamyar 
Published: December 2011

Summary

Background and objectives
The influence of pretransplant dialysis modality on post-transplant outcomes is not clear. This study examined associations of pretransplant dialysis modality with post-transplant outcomes in a large national cohort of kidney transplant recipients.

Design, setting, participants, & measurements
Linking the 5-year patient data of a large dialysis organization to the Scientific Registry of Transplant Recipients, 12,416 hemodialysis and 2092 peritoneal dialysis patients who underwent first kidney transplantation were identified. Mortality or graft failure and delayed graft function risks were estimated by Cox regression (hazard ratio) and logistic regression (odds ratio), respectively.

Results
Recipients treated with peritoneal dialysis pretransplantation had lower (21.9/1000 patient-years [95% confidence interval: 18.1–26.5]) crude all-cause mortality rate than those recipients treated with hemodialysis (32.8/1000 patient-years [30.8–35.0]). Pretransplant peritoneal dialysis use was associated with 43% lower adjusted all-cause and 66% lower cardiovascular death. Furthermore, pretransplant peritoneal dialysis use was associated with 17% and 36% lower unadjusted death-censored graft failure and delayed graft function risk, respectively. However, after additional adjustment for relevant covariates, pretransplant peritoneal dialysis modality was not a significant predictor of death-censored graft failure delayed graft function, respectively. Similar trends were noted on analyses using a propensity score matched cohort of 2092 pairs of patients.

Conclusions
Compared with hemodialysis, patients treated with peritoneal dialysis before transplantation had lower mortality but similar graft loss or delayed graft function. Confounding by residual selection bias cannot be ruled out.