bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficient Blockade of Akt signaling is a determinant factor to overcome resistance to Matuzumab
Authors: Meira Debora D , Almeida Vitor H , Mororó Jânio S , Caetano Mauricio S , Nóbrega Isabel P , Batista Delano , Sternberg Cinthya , Ferreira Carlos G 
Published: December 2011

Abstract

Background
Clinical studies have shown antineoplastic effectiveness of monoclonal antibodies (MAbs) against EGFR for different indications. Several MAbs directed to EGFR were developed recently, such as matuzumab, but there is still lack of information on preclinical data on its combination with chemo-radiation. Thus, the present study intended to examine the molecular pathways triggered by matuzumab alone or associated to chemo-radiotherapy in gynecological cell lines and its impact on cell growth and signaling.

Results
Combination of matuzumab with radiation and cisplatin did not enhance its cytostatic effects on A431, Caski and C33A cells (high, intermediate and low EGFR expression, respectively) in clonogenic assays, when compared to controls. The lack of effect was mediated by persistent signaling through EGFR due to its impaired degradation. In spite of the fact that matuzumab inhibited phosphorylation of EGFR, it had no effect upon cell viability. To analyze which downstream molecules would be involved in the EGFR signaling in the presence of matuzumab, we have tested it in combination with either PD98059 (MAPK inhibitor), or LY294002 (PI3K inhibitor). Matuzumab exhibited a synergic effect with LY294002, leading to a reduction of Akt phosphorylation that was followed by a decrease in A431 and Caski cells survival. The combination of PD98059 and matuzumab did not show the same effect suggesting that PI3K is an important effector of EGFR signaling in matuzumab-treated cells. Nonetheless, matuzumab induced ADCC in Caski cells, but not in the C33A cell line, suggesting that its potential therapeutic effects in vitro are indeed dependent on EGFR expression.

Conclusions
Matuzumab combined with chemoradiation did not induce cytotoxic effects on gynecological cancer cell lines in vitro, most likely due to impaired EGFR degradation. However, a combination of matuzumab and PI3K inhibitor synergistically inhibited pAkt and cell survival, suggesting that the use of PI3K/Akt inhibitors could overcome intrinsic resistance to matuzumab in vitro. Altogether, data presented here can pave the way to a rational design of clinical strategies in patients with resistant profile to anti-EGFR inhibitors based on combination therapy.
The Relationship between Brown Adipose Tissue Activity and Neoplastic Status: an 18F-FDG PET/CT Study in the Tropics
Authors: Huang Yung-Cheng , Chen Tai-Been , Hsu Chien-Chin , Li Shau-Hsuan , Wang Pei-Wen , Lee Bi-Fang , Kuo Ching-Yuan , Chiu Nan-Tsing 
Published: December 2011

Abstract

Background
Brown adipose tissue (BAT) has thermogenic potential. For its activation, cold exposure is considered a critical factor though other determinants have also been reported. The purpose of this study was to assess the relationship between neoplastic status and BAT activity by 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) in people living in the tropics, where the influence of outdoor temperature was low.

Methods

18F-FDG PET/CT scans were reviewed and the total metabolic activity (TMA) of identified activated BAT quantified. The distribution and TMA of activated BAT were compared between patients with and without a cancer history. The neoplastic status of patients was scored according to their cancer history and 18F-FDG PET/CT findings. We evaluated the relationships between the TMA of BAT and neoplastic status along with other factors: age, body mass index, fasting blood sugar, gender, and outdoor temperature.

Results
Thirty of 1740 patients had activated BAT. Those with a cancer history had wider BAT distribution (p = 0.043) and a higher TMA (p = 0.028) than those without. A higher neoplastic status score was associated with a higher average TMA. Multivariate analyses showed that neoplastic status was the only factor significantly associated with the TMA of activated BAT (p = 0.016).

Conclusions
Neoplastic status is a critical determinant of BAT activity in patients living in the tropics. More active neoplastic status was associated with more vigorous TMA of BAT.
A Novel Approach to Standard Techniques in the Assessment and Quantification of the Interventricular Systolic Relationship
Authors: Bruhl Steven R , Chahal Mangeet , Khouri Samer J 
Published: December 2011

Abstract

Background
Blood flow between the right and left ventricles is subject to the continuity equation and systolic ventricular interdependence. Quantification of this relationship might aid in understanding inter-ventricular function. The purpose of this study was to evaluate and quantify ventricular interdependence by directly comparing right and left ventricular systolic function though echocardiographic surrogates of right and left ventricular systolic function such as MAPSE, TAPSE, RV TVI and LV TVI.

Methods
This study prospectively evaluated 51 healthy participants (mean age, 41 ± 17 years) by resting echocardiography. In addition to standard measurements, tricuspid annular plane of systolic excursion, (TAPSE), mitral annular plane of systolic excursion (MAPSE), and the peak annulus systolic velocity of the right ventricular (RVs) and left ventricular (LVs) free walls were measured by M-mode and pulsed wave Doppler tissue echocardiography and further evaluated for variance across age, gender, and body surface area.

Results
TAPSE (22.1 ± 2.9 mm) was over 54.5% greater than MAPSE (14.3 ± 2.6 mm) and RVs was 64.4% greater than LVs. The LV to RV systolic relationship measured by MAPSE/TAPSE and LVs/RVs ratios were 0.66 ± 0.14 and 0.76 ± 0.21 respectively. These values were not significantly affected by age, gender or body surface area (BSA).

Conclusion
MAPSE/TAPSE and LVs/RVs ratios appear stable across age, gender, and BSA potentially making them good surrogates of systolic ventricular relationship and interdependence.
Determinants of quality of life in adults with type 1 and type 2 diabetes
Authors: Imayama Ikuyo , Plotnikoff Ronald C , Courneya Kerry S , Johnson Jeffrey A 
Published: December 2011

Abstract

Background
Limited evidence exists on the determinants of quality of life (QoL) specific to adults with type 1 diabetes (T1D). Further, it appears no study has compared the determinants of QoL between T1D and type 2 diabetes (T2D) groups. The objectives of this study were to examine: (1) determinants of QoL in adults with T1D; and, (2) differences in QoL determinants between T1D and T2D groups.

Methods
The Alberta Longitudinal Exercise and Diabetes Research Advancement (ALEXANDRA) study, a longitudinal study of adults with diabetes in Alberta, Canada. Adults (18 years and older) with T1D (N = 490) and T2D (N = 1,147) provided information on demographics (gender, marital status, education, and annual income), personality (activity trait), medical factors (diabetes duration, insulin use, number of comorbidities, and body mass index), lifestyle behaviors (smoking habits, physical activity, and diet), health-related quality of life (HRQL) and life satisfaction. Multiple regression models identified determinants of HRQL and life satisfaction in adults with T1D. These determinants were compared with determinants for T2D adults reported in a previous study from this population data set. Factors significantly associated with HRQL and life satisfaction in either T1D or T2D groups were further tested for interaction with diabetes type.

Results
In adults with T1D, higher activity trait (personality) score (β = 0.28, p < 0.01), fewer comorbidities (β = - 0.27, p < 0.01), lower body mass index (BMI)(β = - 0.12, p < 0.01), being a non-smoker (β = - 0.14, p < 0.01), and higher physical activity levels (β = 0.16, p < 0.01) were associated with higher HRQL. Having a partner (β = 0.11, p < 0.05), high annual income (β = 0.16, p < 0.01), and high activity trait (personality) score (β = 0.27, p < 0.01) were significantly associated with higher life satisfaction. There was a significant age × diabetes type interaction for HRQL. The T2D group had a stronger positive relationship between advancing age and HRQL compared to the T1D group. No interaction was significant for life satisfaction.

Conclusions
Health services should target medical and lifestyle factors and provide support for T1D adults to increase their QoL. Additional social support for socioeconomically disadvantaged individuals living with this disease may be warranted. Health practitioners should also be aware that age has different effects on QoL between T1D and T2D adults.
An SNR-based admission control scheme in WiFi-based vehicular networks
Authors: Kim Kihun , Kim Younghyun , Pack Sangheon , Choi Nakjung 
Published: December 2011

Abstract
In WiFi-based vehicular networks, the performance anomaly problem can be serious because different vehicles with diverse channel conditions access the channel by a random access protocol. In this article, we first develop a novel analytical model, which combines the vehicular traffic theory and WiFi properties to show the impact of performance anomaly at the intersection. We then propose a signal-to-noise ratio (SNR)-based admission control scheme that excludes vehicles with bad channel qualities to address the performance anomaly problem. Extensive simulation and analytical results are presented to show the effect of the traffic condition and the topology. From the simulation results, it can be found that the SNR-based admission control scheme can improve the overall throughput, and starvation issues can be addressed by means of mobility in WiFi-based vehicular networks with multiple intersections.
Hierarchical convergence of an implicit double-net algorithm for nonexpansive semigroups and variational inequality problems
Authors: Yao Yonghong , Je Cho Yeol , Liou Yeong-Cheng 
Published: December 2011

AbstractIn this paper, we show the hierarchical convergence of the following implicit double-net algorithm:

x

s
,
t

=
s

[

t
f

(

x

s
,
t

)

+

(

1
-
t

)

(

x

s
,
t

-
μ
A

x

s
,
t

)

]

+

(

1
-
s

)

1

λ

s

∫

0

λ

s

T

(

v

)

x

s
,
t

d
ν
,

∀
s
,
t
∈

(

0
,
1

)

,

where f is a ρ-contraction on a real Hilbert space H, A : H → H is an α-inverse strongly monotone mapping and S = {T(s)}s ≥ 0: H → H is a nonexpansive semi-group with the common fixed points set Fix(S) ≠ ∅, where Fix(S) denotes the set of fixed points of the mapping S, and, for each fixed t ∈ (0, 1), the net {x
s, t
} converges in norm as s → 0 to a common fixed point x
t
∈ Fix(S) of {T(s)}s ≥ 0and, as t → 0, the net {x
t
} converges in norm to the solution x* of the following variational inequality:

x

*

∈
F
i
x

(

S

)

;

〈

A

x

*

,

x
-

x

*

〉

≥
0
,

∀
x
∈
F
i
x

(

S

)

.

MSC(2000): 49J40; 47J20; 47H09; 65J15.
Learning in a simple biological system: a pilot study of classical conditioning of human macrophages in vitro
Authors: Nilsonne Gustav , Appelgren Alva , Axelsson John , Fredrikson Mats , Lekander Mats 
Published: December 2011

Abstract
Recent advances in cell biology and gene regulation suggest mechanisms whereby associative learning could be performed by single cells. Therefore, we explored a model of classical conditioning in human macrophages in vitro. In macrophage cultures, bacterial lipopolysaccharide (LPS; unconditioned stimulus) was paired once with streptomycin (conditioned stimulus). Secretion of interleukin-6 (IL-6) was used as response measure. At evocation, conditioning was not observed. Levels of IL-6 were higher only in those cultures that had been exposed to LPS in the learning phase (p's < .05), regardless whether they received the conditioned stimulus or not at evocation.
However, habituation was evident, with a 62% loss of the IL-6 response after three LPS presentations (p < .001). If further experiments confirm that simple learning can occur in immune cells, this may have bearings not only on immune regulation, but also on the brain response to molecular signals detected in the periphery. Importantly, whether capacities for simple learning in single cells extend beyond habituation, and how this would be demonstrated, remain open questions.
Extraosseous (extramedullary) plasmacytomas: a clinicopathologic and immunophenotypic study of 32 Chinese cases
Authors: Zuo Zhuo , Tang Yuan , Bi Cheng-Feng , Zhang Wen-Yan , Zhao Sha , Wang Xiao-Qing , Yang Qun-Pei , Zou Li-Qun , Liu Wei-Ping 
Published: December 2011

AbstractBackgroundExtraosseous plasmacytoma, so called extramedullary plasmacytoma (EMP) is relatively rare in China. The aim was investigate the clinicopathologic features of EMP and the role of Immunophenotype and genotype detection in diagnosis of EMP.MethodsThirty-two cases of EMP were investigated retrospectively by histopathology, immunophenotype, genotype and survival analysis.ResultsClinically, the mean age of the patients was 53.4. Most of the patients received no treatment after the diagnosis was established, and the prognosis was relatively poor. Histologically, in 40% of the cases, the neoplastic cells were grade II or III. The neoplastic cells expressed one or more PC associated antigens. The immunophenotype of EMP and inflammation of sinonasal regions with numerous PC infiltrations were compared and showed some difference in expression of CD45, CD27, CD44v6 and Bcl-2 as well. Ig light chain restriction was detected in 87.5% of the cases.Conclusionswe described 32 Chinese cases of EMP, compare with that reported in the literature, some differences are presented, including higher percentage of grade II and III cases, clinically inconsistent treatment and management as well as poor outcome of the disease.
Reverse protection assay: a tool to analyze transcriptional rates from individual promoters
Authors: Zubo Yan O , Kusnetsov Victor V , Börner Thomas , Liere Karsten 
Published: December 2011

Abstract
Transcriptional activity of entire genes in chloroplasts is usually assayed by run-on analyses. To determine not only the overall intensity of transcription of a gene, but also the rate of transcription from a particular promoter, we created the Reverse RNase Protection Assay (RePro): in-organello run-on transcription coupled to RNase protection to define distinct transcript ends during transcription. We demonstrate successful application of RePro in plastid promoter analysis and transcript 3' end processing.
The Scandinavian multicenter hemodynamic evaluation of the SJM Regent aortic valve
Authors: Offstad Jon , Andersen Kai , Paulsson Per , Andreasson Jesper , Kjellman Ulf , Lundblad Oluf , Engstrøm Karl Gunnar , Haaverstad Rune , Svennevig Jan L 
Published: December 2011

Abstract

Background
112 patients who received small and medium sized St.Jude Regent heart valves (19-25 mm) at 7 Scandinavian centers were studied between January 2003 and February 2005 to obtain non-invasive data regarding the hemodynamic performance at rest and during Dobutamine stress echocardiography (DSE) testing one year after surgery.

Material and methods
46 woman and 66 men, aged 61.8 ± 9.7 (18-75) years, were operated on for aortic regurgitation (17), stenosis (65), or mixed dysfunction (30). Valve sizes were 19 mm (6), 21 mm (33), 23 mm (41), 25 mm (30). Two patients receiving size 27 valves were excluded from the hemodynamic evaluation. Pledgets were used in 100 patients, everted mattress in 66 and simple interrupted sutures in 21. Valve orientation varied and was dependent on the surgeons' choice. 34 patients (30.4%) underwent concomitant coronary artery surgery.

Results
There were two early deaths (1.8%) and three late deaths, one because of pancreatic cancer. Late events during follow-up were: non structural dysfunction (1), bleeding (2), thromboembolism (2). At one year follow up 93% of the patients were in NYHA classes 1-2 versus 47.8% preoperatively.
Dobutamine stress echocardiography (DSE) was performed in a total of 66 and maximal peak stress was reached in 61 patients.
During DSE testing, the following statistically significant changes took place: Heart rate increased by 73.0%, cardiac output by 85.5%, left ventriclular ejection fraction by 19.6%, and maximal mean prosthetic transvalvular gradient by 133.8%, whereas the effective orifice area index did not change.
Left ventricular mass fell during one year from 215 ± 63 to 197 ± 62 g (p < 0.05).

Conclusion
The Dobutamine test induces a substantial stress, well suitable for echocardiographic assessment of prosthesis valve function and can be performed in the majority of the patients. The changes in pressure gradients add to the hemodynamic characteristics of the various valve sizes.
In our patients the St. Jude Regent valve performed satisfactory at rest and under pharmacological stress situation.
Microglial p38α MAPK is critical for LPS-induced neuron degeneration, through a mechanism involving TNFα
Authors: Xing Bin , Bachstetter Adam D , Van Eldik Linda J 
Published: December 2011

AbstractBackgroundThe p38α MAPK isoform is a well-established therapeutic target in peripheral inflammatory diseases, but the importance of this kinase in pathological microglial activation and detrimental inflammation in CNS disorders is less well understood. To test the role of the p38α MAPK isoform in microglia-dependent neuron damage, we used primary microglia from wild-type (WT) or p38α MAPK conditional knockout (KO) mice in co-culture with WT cortical neurons, and measured neuron damage after LPS insult.ResultsWe found that neurons in co-culture with p38α-deficient microglia were protected against LPS-induced synaptic loss, neurite degeneration, and neuronal death. The involvement of the proinflammatory cytokine TNFα was demonstrated by the findings that p38α KO microglia produced much less TNFα in response to LPS compared to WT microglia, that adding back TNFα to KO microglia/neuron co-cultures increased the LPS-induced neuron damage, and that neutralization of TNFα in WT microglia/neuron co-cultures prevented the neuron damage. These results using cell-selective, isoform-specific KO mice demonstrate that the p38α MAPK isoform in microglia is a key mediator of LPS-induced neuronal and synaptic dysfunction. The findings also provide evidence that a major mechanism by which LPS activation of microglia p38α MAPK signaling leads to neuron damage is through up-regulation of the proinflammatory cytokine TNFα.ConclusionsThe data suggest that selective targeting of p38α MAPK signaling should be explored as a potential therapeutic strategy for CNS disorders where overproduction of proinflammatory cytokines is implicated in disease progression.
Correlation between carboxylesterase alleles and insecticide resistance in Culex pipiens complex from China
Authors: Liu Yangyang , Zhang Hanying , Qiao Chuanling , Lu Xiping , Cui Feng 
Published: December 2011

Abstract

Background
In China, large amounts of chemical insecticides are applied in fields or indoors every year, directly or indirectly bringing selection pressure on vector mosquitoes. Culex pipiens complex has evolved to be resistant to all types of chemical insecticides, especially organophosphates, through carboxylesterases. Six resistant carboxylesterase alleles (Ester) were recorded previously and sometimes co-existed in one field population, representing a complex situation for the evolution of Ester genes.

Results
In order to explore the evolutionary scenario, we analyzed the data from an historical record in 2003 and a recent investigation on five Culex pipiens pallens populations sampled from north China in 2010. Insecticide bioassays showed that these five populations had high resistance to pyrethroids, medium resistance to organophosphates, and low resistance to carbamates. Six types of Ester alleles, Ester

B1
, Ester

2
, Ester

8
, Ester

9
, Ester

B10
, and Ester

11
were identified, and the overall pattern of their frequencies in geographic distribution was consistent with the report seven years prior to this study. Statistical correlation analysis indicated that Ester

8
and Ester

9
positively correlated with resistance to four insecticides, and Ester

B10
to one insecticide. The occurrences of these three alleles were positively correlated, while the occurrence of Ester

B1
was negatively correlated with Ester

8
, indicating an allelic competition.

Conclusion
Our analysis suggests that one insecticide can select multiple Ester alleles and one Ester allele can work on multiple insecticides. The evolutionary scenario of carboxylesterases under insecticide selection is possibly "one to many".
MEIS1, PREP1, and PBX4 Are Differentially Expressed in Acute Lymphoblastic Leukemia: Association of MEIS1 Expression with Higher Proliferation and Chemotherapy Resistance
Authors: Rosales-Aviña Judith A , Torres-Flores Jorge , Aguilar-Lemarroy Adriana , Gurrola-Díaz Carmen , Hernández-Flores Georgina , Ortiz-Lazareno Pablo C , Lerma-Díaz José M , de Celis Ruth , González-Ramella Óscar , Barrera-Chaires Esperanza , Bravo-Cuellar Alejandro , Jave-Suárez Luis F 
Published: December 2011

AbstractBackgroundThe Three-amino acid-loop-extension (TALE) superfamily of homeodomain-containing transcription factors have been implicated in normal hematopoiesis and in leukemogenesis and are important survival, differentiation, and apoptosis pathway modulators. In this work, we determined the expression levels ofTALEgenes in leukemic-derived cell lines, in blood samples of patients with Acute lymphoblastic leukemia (ALL), and in the blood samples of healthy donors.ResultsHere we show increased expression ofMEIS1, MEIS2,andPREP1genes in leukemia-derived cell lines compared with blood normal cells. High levels ofMEIS1andPREP1, and low levels ofPBX4expression were also founded in samples of patients with ALL. Importantly, silencing ofMEIS1decreases the proliferation of leukemia-derived cells but increases their survival after etoposide treatment. Etoposide-induced apoptosis induces down-regulation of MEIS1 expression orPREP1up-regulation in chemotherapy-resistant cells.ConclusionsOur results indicate that up-regulation ofMEIS1is important for sustaining proliferation of leukemic cells and that down-regulation ofMEIS1or up-regulation ofPREP1andPBXgenes could be implicated in the modulation of the cellular response to chemotherapeutic-induced apoptosis.