bluuebunny/crossref_metadata_2025 huggingface dataset:
Aleurites moluccana (L.) Willd. Leaves: Mechanical Antinociceptive Properties of a Standardized Dried Extract and Its Chemical Markers
Authors: Quintão Nara L. M. , Meyre-Silva Christiane , Silva Gislaine F. , Antonialli Carla S. , Rocha Lilian W. , Lucinda-Silva Ruth M. , Malheiros Angela , Souza Márcia M. , Cechinel Filho Valdir , Bresolin Tania M. B.
Published: April 2011

Seeking to develop a new analgesic phytomedicine, a spray‐dried extract (SDE) of Aleurites moluccana (L.) Willd. leaves was developed in scale up (5 kg). The SDE was standardized at 3% w/w in relation to the flavonoid 2′′‐O‐rhamnosylswertisin. The SDE batches were evaluated in relation to their physical, physiochemical, and pharmacological characteristics. The results demonstrated the reproducibility of the scale up SDE process which, when dosed orally, reduced carrageenan‐induced mechanical hypernociception, with an ID50% of 443 mg/kg. Similar results were obtained with animals injected with complete Freund′s adjuvant (CFA), in which SDE caused inhibition of 48 ± 4%. SDE was effective in preventing prostaglandin E2 (PGE2)‐induced mechanical hypernociception (inhibition of 26 ± 10% and 33 ± 3%, at 250 and 500 mg/kg, respectively). Swertisin and 2′′‐O‐rhamnosylswertisin isolated from the own extract were effective in inhibiting the hypernociceptive response induced by carrageenan (70 ± 2% and 50 ± 5%, resp.). Furthermore, 2′′‐O‐rhamnosylswertisin was capable of significantly inhibiting the mechanical sensitization induced by CFA or PGE2, with inhibitions of 25 ± 3% and 94 ± 6%, respectively. These results suggest that the effects of SDE are related, at least in part, to the presence of these flavonoids.
Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Events: A Meta-Analysis of Randomized Clinical Trials
Authors: Monami Matteo , Cremasco Francesco , Lamanna Caterina , Colombi Claudia , Desideri Carla Maria , Iacomelli Iacopo , Marchionni Niccolò , Mannucci Edoardo
Published: April 2011

Objective. Data from randomized clinical trials with metabolic outcomes can be used to address concerns about potential issues of cardiovascular safety for newer drugs for type 2 diabetes. This meta-analysis was designed to assess cardiovascular safety of GLP-1 receptor agonists.Design and Methods. MEDLINE, Embase, and Cochrane databases were searched for randomized trials of GLP-1 receptor agonists (versus placebo or other comparators) with a duration ≥12 weeks, performed in type 2 diabetic patients. Mantel-Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for major cardiovascular events (MACE), on an intention-to-treat basis, excluding trials with zero events.Results. Out of 36 trials, 20 reported at least one MACE. The MH-OR for all GLP-1 receptor agonists was 0.74 (0.50–1.08),P=.12(0.85 (0.50–1.45),P=.55, and 0.69 (0.40–1.22),P=.20, for exenatide and liraglutide, resp.). Corresponding figures for placebo-controlled and active comparator studies were 0.46 (0.25–0.83),P=.009, and 1.05 (0.63–1.76),P=.84, respectively.Conclusions. To date, results of randomized trials do not suggest any detrimental effect of GLP-1 receptor agonists on cardiovascular events. Specifically designed longer-term trials are needed to verify the possibility of a beneficial effect.
Training the Trainees in Radiation Oncology with Telemedicine as a Tool in a Developing Country: A Two-Year Audit
Authors: Agrawal Sushma , Maurya Anil Kumar , Shrivastava Kirti , Kumar Shaleen , Pant M. C. , Mishra Saroj Kant
Published: April 2011

Purpose. The estimated new cancer patient load in the Indian state of Uttar Pradesh is 0.1–0.12 million per year. Approximately two thirds of these require treatment by a radiation oncologist. Radiation oncologists: cancer patient ratio in this state is 1 : 2000 as compared to the recommended 1 : 250. This problem is compounded by the poor infrastructure of radiation oncology departments in the state which is suboptimal for teaching, training of resident doctors, and treatment in most barring a few departments. To bridge some gap in the sociodemographics stated above and enhancement of training of residents, we submitted a project for establishment of a telemedicine facility in our department to the Department of Science and Technology, Government of India. We present the design, implementation, and a two-year audit of our tele-education activities.Materials and Methods. After the sanction of the project, we established telemedicine linkage with another medical institute in the city located 25 kms away in 2007. After implementation of the project, academic sessions designed for trainee residents in our department were shared with the remote end. A record of these activities and a feedback of the activities were audited at the end of 2 years of implementation of this project.Results. Regular videoconferencing sessions comprising of lectures on clinical oncology, medical physics, and radiobiology were held. Feedback from the users revealed satisfaction with the content of the academic sessions for the purpose of MD training.Conclusions. Distance education in radiation oncology is an important tool for training of the trainee residents.
Strong Convergence Theorems for Families of Weak Relatively Nonexpansive Mappings
Authors: Shehu Yekini
Published: April 2011

We construct a new Halpern type iterative scheme by hybrid methods and prove strong
convergence theorem for approximation of a common fixed point of two countable families of weak relatively
nonexpansive mappings in a uniformly convex and uniformly smooth real Banach space using the properties of
generalized f‐projection operator. Using this result, we discuss strong convergence theorem concerning general
H‐monotone mappings. Our results extend many known recent results in the literature.
Review of Evidence Suggesting That the Fascia Network Could Be the Anatomical Basis for Acupoints and Meridians in the Human Body
Authors: Bai Yu , Wang Jun , Wu Jin-peng , Dai Jing-xing , Sha Ou , Tai Wai Yew David , Yuan Lin , Liang Qiu-ni
Published: April 2011

The anatomical basis for the concept of meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the evidence supporting a relationship between acupuncture points/meridians and fascia. The reviewed evidence supports the view that the human body′s fascia network may be the physical substrate represented by the meridians of TCM. Specifically, this hypothesis is supported by anatomical observations of body scan data demonstrating that the fascia network resembles the theoretical meridian system in salient ways, as well as physiological, histological, and clinical observations. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.
Capsule Endoscopy in Patients with Cardiac Pacemakers, Implantable Cardioverter Defibrillators, and Left Heart Devices: A Review of the Current Literature
Authors: Bandorski Dirk , Keuchel Martin , Brück Martin , Hoeltgen Reinhard , Wieczorek Marcus , Jakobs Ralf
Published: April 2011

Background and Study Aims. Capsule endoscopy is an established tool for investigation of the small intestine. Because of limited clinical experience in patients with cardiac devices, the Food and Drug Administration and the manufacturer recommended not to use capsule endoscopy in these patients. The vast majority of investigations did not reveal any interference between capsule endoscopy and cardiac devices. Methods. Studies investigating interference between CE and cardiac devices were analysed. For the review we considered studies published in English or German and indexed in Medline, as well as highly relevant abstracts. Results. In vitro and in vivo studies mainly revealed no interference between capsule endoscopy and cardiac devices. Technical data of capsule endoscopy (Given Imaging) reveal that interference with cardiac pacemakers and implantable cardioverter defibrillator is impossible. Telemetry can interfere with CE video. Conclusion. The clinical use of capsule endoscopy (Given Imaging) is unproblematic in patients with cardiac pacemakers.
Treatment of Recurrent Focal Segmental Glomerulosclerosis in Pediatric Kidney Transplant Recipients: Effect of Rituximab
Authors: Sethna Christine , Benchimol Corinne , Hotchkiss Hilary , Frank Rachel , Infante Lulette , Vento Suzanne , Trachtman Howard
Published: April 2011

Recurrence of focal segmental glomerulosclerosis (FSGS) after renal transplantation is a complication that often leads to graft loss. There is no consensus on the optimal treatment of recurrent FSGS. Rituximab, a monoclonal antibody to CD20, may be a useful treatment of this complication.Methods. We report four pediatric cases of recurrent FSGS treated with rituximab and plasmapheresis.Results. Four children (2M/2F), age 15.3 ± 2.6, with recurrent FSGS posttransplant were identified. Four doses of rituximab were administered 171 ± 180 days posttransplant and 114 ± 169 days after the start of plasmapheresis. Three children responded with complete remission, one of whom relapsed after four months. One child had a partial response with a decrease in proteinuria that was not sustained. No adverse side effects were reported during treatment or followup (mean 22.5 months).Conclusions. Rituximab is a safe and well-tolerated ancillary treatment for recurrent FSGS in pediatric patients in conjunction with plasmapheresis.
Identifiability for a Class of Discretized Linear Partial Differential Algebraic Equations
Authors: Cantó Begoña , Coll Carmen , Sánchez Elena
Published: April 2011

This paper presents the use of an iteration method to solve the identifiability problem for a class of discretized linear partial differential algebraic equations. This technique consists in replacing the partial derivatives in the PDAE by differences and analyzing the difference algebraic equations obtained. For that, the theory of discrete singular systems, which involves Drazin inverse matrix, is used. This technique can also be applied to other differential equations in mathematical physics.
Characterization and Electrocatalytic Properties of Titanium-Based Ru0.3Co0.7−xCexMixed Oxide Electrodes for Oxygen Evolution in Alkaline Solution
Authors: Wu Hongjun , Ruan Qin , Li Li , Wang Baohui
Published: April 2011

Ti-supported RuO2-Co3O4-CeO2(Ru0.3Co0.7−xCexoxide,0≤x≤0.7) electrodes were prepared by sol-gel process. The phase structure, surface morphology, and microstructure of the oxide layer were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Electrocatalytic activity and oxygen evolution reaction (OER) kinetics on these electrodes in 1.0 mol⋅dm−3KOH solution were studied by recording open-circuit potential, cyclic voltammetry, and polarisation curves. The results showed that the appropriate content of CeO2could reduce the grain size and increase active surface area. The electrocatalytic activity shows a strong dependence on the CeO2content in the film. Catalytic performance of mixed oxide electrodes with 40 mol % CeO2was the best, with the greatest voltammetric charge, 86.23 mC⋅cm−2, and the smallest apparent activation energy for OER at 0.60 V was 22.76 kJ⋅mol−1.
Multicenter Study of Buruli Ulcer Disabilities in the Head and Neck Region
Authors: Agbenorku Pius
Published: April 2011

Objective. To identify disabilities caused by Buruli Ulcer Disease (BUD) when it affects the Head and Neck Region (HNR) of patients in endemic areas and suggest possible ways to overcome the complications involved. Methods. Data for the study was collected from six different hospitals in the central part of Ghana from 2004–2009. Diagnosis of BUD was based on clinical findings and confirmed by positive result of Ziehl-Neelson Test for Acid Fast Bacilli, Polymerase Chain Reaction, or Histopathology. Treatment of BUD involved a combination of surgical interventions and antimycobacterial chemotherapy for 8 weeks. Results. The age of the 38 patients ranged from 0–56 years (mean age of 14.3 years), with males outnumbering females. Most (55.3%, ) of the patients reported to the facilities with developed BUD deformities. Patients who lost their eyeball () recorded the highest in terms of functional disability. A mean total hospital stay of 52 days and follow-up period of 2.3 years were recorded for the study. Conclusion. Visual impairment was the commonest form of disability recorded in the HNR. Management difficulties and BUD disabilities could be avoided by early detection of the disease and training of health professionals at district levels.
Optical and Thermal Properties of In2S3
Authors: Saadallah Faycel , Jebbari Neila , Kammoun Najoua , Yacoubi Noureddine
Published: April 2011

Photothermal deflection spectroscopy (PDS) is carried out in order to investigate thermal and optical properties of Al doped In2S3. The influence of thermal annealing on its gap energy as well as its thermal properties is revealed. In this way, we notice that thermal conductivity is increased and the gap energy is reduced. These features are probably due to the improvement of the crystalline structure of the sample.
Arginase and Arginine Dysregulation in Asthma
Authors: Benson Renée C. , Hardy Karen A. , Morris Claudia R.
Published: April 2011

In recent years, evidence has accumulated indicating that the enzyme arginase, which converts L-arginine into L-ornithine and urea, plays a key role in the pathogenesis of pulmonary disorders such as asthma through dysregulation of L-arginine metabolism and modulation of nitric oxide (NO) homeostasis. Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and remodeling. Through substrate competition, arginase decreases bioavailability of L-arginine for nitric oxide synthase (NOS), thereby limiting NO production with subsequent effects on airway tone and inflammation. By decreasing L-arginine bioavailability, arginase may also contribute to the uncoupling of NOS and the formation of the proinflammatory oxidant peroxynitrite in the airways. Finally, arginase may play a role in the development of chronic airway remodeling through formation of L-ornithine with downstream production of polyamines and L-proline, which are involved in processes of cellular proliferation and collagen deposition. Further research on modulation of arginase activity and L-arginine bioavailability may reveal promising novel therapeutic strategies for asthma.
A Comprehensive Approach to Power Management in Embedded Systems
Authors: Fröhlich Antônio Augusto
Published: April 2011

Power management is addressed in the context of embedded systems from energy-aware design to energy-efficient implementation. A set of mechanisms specifically conceived for this scenario is proposed, including a power management API defined at the level of user-visible system components, the infrastructure necessary to implement that API (namely, battery monitoring, accounting, autosuspend, and autoresume), an energy-event propagation mechanism based on Petri nets and implemented with aspect-oriented programming techniques, and an autonomous power manager build upon the proposed API and infrastructure. These mechanisms are illustrated and evaluated using realistic wireless sensor network cases that sustain comparisons with other proposals at each of the considered levels. As a result, this paper has its main contribution on the introduction of a comprehensive and systematic way to deal with power management issues in resource-constrained, battery-operated systems.
Testosterone Increases: Sodium Reabsorption, Blood Pressure, and Renal Pathology in Female Spontaneously Hypertensive Rats on a High Sodium Diet
Authors: Liu Bei , Ely Daniel
Published: April 2011

Estrogen (E) and testosterone (T) are important in the sexually dimorphic pattern of blood pressure (BP) development. The goal was to examine the effects of endogenous E and exogenous T in the development of hypertension in female spontaneously hypertensive rats (SHR) on a high sodium diet. Female SHR (, 5-week) were divided into four groups: (1) control (), (2) ovariectomized (OVX, ), (3) testosterone implants with intact ovaries (T, ), and (4) ovariectomized + testosterone implants (OVX+T, ). T was given immediately after OVX and replaced every two weeks and they were fed a 3% NaCl diet. BP was measured weekly and plasma norepinephrine (NE) analyzed by HPLC. OVX+T females exhibited the greatest elevation in BP (190 ± 4.0 mmHg) compared to controls at 15 weeks of age (140 ± 3.4 mmHg, ) and a pattern of hypertension development similar to that of male SHR. Females with T treatment showed evidence of glomerulosclerosis. In conclusion, T accelerated the development of hypertension similar to the BP pattern observed in males; the presence of ovaries attenuated the T induced increase in BP; T increased renal sodium reabsorption, and T increased glomerulosclerosis.
Steady Heat Transfer through a Two‐Dimensional Rectangular Straight Fin
Authors: Moitsheki Raseelo J. , Rowjee Atish
Published: April 2011

Exact solutions for models describing heat transfer in a two‐dimensional rectangular fin are constructed. Thermal conductivity, internal energy generation function, and heat transfer coefficient are assumed to be dependent on temperature. We apply the Kirchoff transformation on the governing equation. Exact solutions satisfying the realistic boundary conditions are constructed for the resulting linear equation. Symmetry analysis is carried out to classify the internal heat generation function, and some reductions are performed. Furthermore, the effects of physical parameters such as extension factor (the purely geometric fin parameter) and Biot number on temperature are analyzed. Heat flux and fin efficiency are studied.
Enhanced Transport Capabilities via Nanotechnologies: Impacting Bioefficacy, Controlled Release Strategies, and Novel Chaperones
Authors: Panagiotou Thomai , Fisher Robert J.
Published: April 2011

Emerging nanotechnologies have, and will continue to have, a major impact on the pharmaceutical industry. Their influence on a drug's life cycle, inception to delivery, is
rapidly expanding. As the industry moves more aggressively toward continuous
manufacturing modes, utilizing Process Analytical Technology (PAT) and Process
Intensification (PI) concepts, the critical role of transport phenomena becomes elucidated.
The ability to transfer energy, mass, and momentum with directed purposeful outcomes is
a worthwhile endeavor in establishing higher production rates more economically.
Furthermore, the ability to obtain desired drug properties, such as size, habit, and
morphology, through novel manufacturing strategies permits unique formulation control
for optimum delivery methodologies. Bottom-up processing to obtain nano-sized crystals
is an excellent example. Formulation and delivery are intimately coupled in improving
bio-efficacy at reduced loading and/or better controlled release capabilities, minimizing
side affects and providing improved therapeutic interventions. Innovative nanotechnology applications, such as simultaneous targeting, imaging and delivery to tumors, are now possible through use of novel chaperones. Other examples include nanoparticles attachment to T-cells, release from novel hydrogel implants, and functionalized encapsulants. Difficult tasks such as drug delivery to the brain via the blood brain barrier and/or the cerebrospinal fluid are now easier to accomplish.
Immunologic Monitoring of Cellular Responses by Dendritic/Tumor Cell Fusion Vaccines
Authors: Koido Shigeo , Homma Sadamu , Takahara Akitaka , Namiki Yoshihisa , Komita Hideo , Nagasaki Eijiro , Ito Masaki , Nagatsuma Keisuke , Uchiyama Kan , Satoh Kenichi , Ohkusa Toshifumi , Gong Jianlin , Tajiri Hisao
Published: April 2011

Although dendritic cell (DC)‐ based cancer vaccines induce effective antitumor activities in murine models, only limited therapeutic results have been obtained in clinical trials. As cancer vaccines induce antitumor activities by eliciting or modifying immune responses in patients with cancer, the Response Evaluation Criteria in Solid Tumors (RECIST) and WHO criteria, designed to detect early effects of cytotoxic chemotherapy in solid tumors, may not provide a complete assessment of cancer vaccines. The problem may, in part, be resolved by carrying out immunologic cellular monitoring, which is one prerequisite for rational development of cancer vaccines. In this review, we will discuss immunologic monitoring of cellular responses for the evaluation of cancer vaccines including fusions of DC and whole tumor cell.
A Special Class of Univalent Functions in Hele‐Shaw Flow Problems
Authors: Curt Paula , Fericean Denisa
Published: April 2011

We study the time evolution of the free boundary of a viscous fluid for planar flows in Hele‐Shaw cells under injection. Applying methods from the theory of univalent functions, we prove the invariance
in time of Φ‐likeness property (a geometric property which includes starlikeness
and spiral‐likeness) for two basic cases: the inner problem and the
outer problem. We study both zero and nonzero surface tension models.
Certain particular cases are also presented.
Application of a Heat‐ and Steam‐Generating Sheet Increases Peripheral Blood Flow and Induces Parasympathetic Predominance
Authors: Nagashima Yoshinao , Igaki Michihito , Suzuki Atsushi , Tsuchiya Shuichi , Yamazaki Yoshimi , Hishinuma Michiko , Oh-ishi Sachiko , Majima Masataka
Published: April 2011

To promote the practical application of a Japanese traditional medical treatment, such as hot compresses, we developed a plaster‐type warming device consisting of a heat‐ and steam‐generating sheet (HSG sheet). First, we tested its effects when applied to the anterior abdominal wall or lumbar region of women complaining of a tendency towards constipation. Application of the sheet to either region produced a feeling of comfort in the abdomen, as assessed by a survey of the subjects. The significant increases in the total hemoglobin observed in these regions suggested an increase in peripheral blood flow, and significant increases in the HF component on ECG and in the amplitude of gastric motility suggested parasympathetic predominance. We concluded that application of the HSG sheet improves the peripheral hemodynamics and autonomic regulation, induces a feeling of comfort in the abdomen, and provides a beneficial environment for the improvement of gastrointestinal movements.
Abstract P5-06-11: Knockdown of Splicing Factor SRp20 Results in Cell Line-Dependent Apoptosis in Breast Cancer Cells
Authors: Ho T-T , Arslan AD , Beck WT , He X.
Published: April 2011

Background: Cancer-specific alternative splicing as well as aberrant splicing factor expression in tumors have been reported (Korner M et al, Am. J. Pathol. 175:461-472, 2009). Splicing factor SRp20 belongs to a family of highly conserved serine-arginine-rich proteins with multiple functions in RNA processing such as spliceosome assembly and alternative splicing (Graveley BR, RNA. 6(9):1197-211, 2000). Materials and Methods: We established stable MDA-MB-231, MCF-7, and T47D cell lines carrying doxycycline (Doxy)-inducible SRp20shRNA and assessed Doxy-induced knockdown (KD) of SRp20 by western blot. We performed cell growth curves in triplicate using the MTT assay to determine the effect of SRp20 KD in these cell lines after Doxy induction of SRp20shRNA, and compared these to controls. For apoptosis assays, we stained SRp20shRNA sublines with Hoechst 33342 and counted apoptotic cells under the microscope. We also carried out western blots to examine the expressions of Bcl-2 and cleaved caspases-3, -6, -7, and -9. Results and Discussion: We found that the expression of SRp20 was upregulated in immortalized human mammary epithelial cells (HMECs), compared to controls, and that the level of SRp20 correlated with the transformation state. Knockdown of SRp20 was seen to be 88%, 58%, and 52% in MDA-MB-231, MCF-7, and T47D cells, respectively. However, SRp20 KD suppressed breast cancer cell growth in a cell line-dependent manner. Cell growth after 7 days was decreased in estrogen receptor-negative (ER-) MDA-MB-231 cells (91.4%), and estrogen receptor-positive (ER+) MCF-7 (73.2%), while SRp20 KD had no effect on growth of ER+ T47D cells. The differences between MCF-7 and T47D were notable, since SRp20 was suppressed by -50% in both lines. We found that the number of apoptotic cells in MDA-MB-231 line remarkably increased after Doxy treatment, indicating that the inhibition of cell growth was due to apoptosis. Further, immunoblot analysis of Bcl-2 and cleaved caspases in MDA-MB-231 cells indicated that the SRp20 KD activates the intrinsic apoptotic pathway in these breast cancer cells. We are presently assessing the expressions of these proteins in MCF-7 and T47D cells and investigating the mechanistic basis for this cell line-dependent effect of SRp20 KD. In summary, we report here a novel finding that inhibition of splicing factor SRp20 inhibits cell growth in some breast cancer cell lines. The intrinsic apoptotic pathway appears to be the main mechanism of cell growth inhibition in these cells. Our results indicate that SRp20 plays a major role in the survival of some breast cancer cell lines. This splicing factor may represent a novel therapeutic target for the treatment of some breast cancers.

(Supported in part by CA40570 and CA138762 from NCI to WTB, in part by IDPH to XH, and in part by UIC)

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-06-11.
Pathogenesis and Consequences of Uniparental Disomy in Cancer
Authors: Makishima Hideki , Maciejewski Jaroslaw P.
Published: April 2011

The systematic application of new genome-wide single nucleotide polymorphism arrays has demonstrated that somatically acquired regions of loss of heterozygosity without changes in copy number frequently occur in many types of cancer. Until recently, the ubiquity of this type of chromosomal defect had gone unrecognized because it cannot be detected by routine cytogenetic technologies. Random and recurrent patterns of copy-neutral loss of heterozygosity, also referred to as uniparental disomy, can be found in specific cancer types and probably contribute to clonal outgrowth owing to various mechanisms. In this review we explore the types, topography, genesis, pathophysiological consequences, and clinical implications of uniparental disomy. Clin Cancer Res; 17(12); 3913–23. ©2011 AACR.
T Cells in Tumors and Blood Predict Outcome in Follicular Lymphoma Treated with Rituximab
Authors: Wahlin Björn Engelbrekt , Sundström Christer , Holte Harald , Hagberg Hans , Erlanson Martin , Nilsson-Ehle Herman , Lindén Ola , Nordström Marie , Østenstad Bjørn , Geisler Christian H. , Brown Peter de Nully , Lehtinen Tuula , Maisenhölder Martin , Tierens Anne M. , Sander Birgitta , Christensson Birger , Kimby Eva
Published: April 2011

Purpose: T cells influence outcome in follicular lymphoma, but their contributions seem to be modified by therapy. Their impact in patients receiving rituximab without chemotherapy is unknown.

Experimental Design: Using flow cytometry, we evaluated the T cells in tumors and/or blood in a total of 250 follicular lymphoma patients included in two Nordic Lymphoma Group randomized trials that compared single rituximab with IFN-α2a–rituximab combinations.

Results: In univariate analysis, higher levels of CD3+, CD4+, and CD8+ T cells in both tumors and blood correlated with superior treatment responses, and in multivariate analysis, tumor-CD3+ (P = 0.011) and blood-CD4+ (P = 0.029) cells were independent. CD4+ cells were favorable regardless of treatment arm, but CD8+ cells were favorable only in patients treated with single rituximab, because IFN-α2a improved responses especially in patients with low CD8+ cell levels. Higher levels of blood-CD3+ (P = 0.003) and blood-CD4+ (P = 0.046) cells predicted longer overall survival, and higher levels of blood-CD8+ cells longer times to next treatment (P = 0.046).

Conclusions: We conclude that therapeutic effects of rituximab are augmented by tumor-associated T cells for rapid responses and by systemic T cells for sustained responses. CD4+ and CD8+ cells are both favorable in patients treated with rituximab. IFN-α2a abrogates the negative impact of few CD8+ cells. Clin Cancer Res; 17(12); 4136–44. ©2011 AACR.
Effective Melanoma Immunotherapy with Interleukin-2 Delivered by a Novel Polymeric Nanoparticle
Authors: Yao Hong , Ng Samuel S. , Huo Long-Fei , Chow Billy K. C. , Shen Zan , Yang Min , Sze Johnny , Ko Otis , Li Ming , Yue Alexander , Lu Li-Wei , Bian Xiu-Wu , Kung Hsiang-Fu , Lin Marie C.
Published: April 2011

Interleukin-2 (IL-2) has been shown to possess antitumor activity in numerous preclinical and clinical studies. However, the short half-life of recombinant IL-2 protein in serum requires repeated high-dose injections, resulting in severe side effects. Although adenovirus-mediated IL-2 gene therapy has shown antitumor efficacy, the host antibody response to adenoviral particles and potential biosafety concerns still obstruct its clinical applications. Here we report a novel nanopolymer for IL-2 delivery, consisting of low molecular weight polyethylenimine (600Da) linked by β-cyclodextrin and conjugated with folate (named H1). H1 was mixed with IL-2 plasmid to form H1/pIL-2 polyplexes of around 100 nm in diameter. Peritumoral injection of these polyplexes suppressed the tumor growth and prolonged the survival of C57/BL6 mice bearing B16–F1 melanoma grafts. Importantly, the antitumor effects of H1/pIL-2 (50 μg DNA) were similar to those of recombinant adenoviruses expressing IL-2 (rAdv-IL-2; 2 × 108 pfu). Furthermore, we showed that H1/pIL-2 stimulated the activation and proliferation of CD8+, CD4+ T cell, and natural killer cells in peripheral blood and increased the infiltration of CD8+, CD4+ Tcells, and natural killer cells into the tumor environment. In conclusion, these results show that H1/pIL-2 is an effective and safe melanoma therapeutic with an efficacy comparable to that of rAdv-IL-2. This treatment represents an alternative gene therapy strategy for melanoma. Mol Cancer Ther; 10(6); 1082–92. ©2011 AACR.
Cancer Cells Cyclically Lose and Regain Drug-Resistant Highly Tumorigenic Features Characteristic of a Cancer Stem-like Phenotype
Authors: He Kaijie , Xu Tong , Goldkorn Amir
Published: April 2011

Drug resistance and brisk tumor initiation have traditionally been viewed as preexisting phenotypes present in small subpopulations of neoplastic cells sometimes termed cancer stem cells. However, recent work in cancer cell lines has shown that drug-resistant tumor-initiating features can emerge de novo within fractionated subpopulations of cells initially lacking these phenotypes. In the present study, we asked whether such phenotypic plasticity exists broadly in unperturbed cancer cell lines and tumor xenografts growing spontaneously without interventions such as drug selection or fractionation into subpopulations used in prior studies. To address this question, we used side population (SP) analysis combined with fluorescence labeling to identify a drug-resistant highly tumorigenic subpopulation and to track and analyze its interaction with the larger phenotypically negative population over time. Remarkably, we observed that SP size fluctuated in a cyclical manner: first contracting via differentiation into the non-SP (NSP) and then reexpanding via simultaneous direct conversion of numerous NSP cells back to the SP phenotype both in culture and in tumor xenografts. These findings show for the first time that adaptive, cancer-promoting traits such as drug resistance and brisk tumor initiation arise not only as solitary events under selective pressures but also as highly orchestrated transitions occurring concurrently in large numbers of cells even without specifically induced drug selection, ectopic gene expression, or fractionation into subpopulations. This high level of coordinated phenotypic plasticity bears consideration when using cancer cell lines as experimental models and may have significant implications for therapeutic efforts targeting cancer stem cells, which are marked by a drug-resistant tumor-initiating phenotype. Mol Cancer Ther; 10(6); 938–48. ©2011 AACR.
Vaginal Tissue Properties versus Increased Intra-Abdominal Pressure: A Preliminary Biomechanical Study
Authors: Martins Pedro A.L.S. , Jorge Renato M. Natal , Ferreia AntÓnio J.M. , Saleme Cristina S. , Roza Thuane , Parente Marco M.P. , Pinotti Marcos , Mascarenhas Teresa , Santos Agostinho , Santos Liliana , Silva-Filho Agnaldo L.
Published: April 2011

Background/Aims: This study aims to evaluate the pelvic floor (PF) tension response during simulated increased intra-abdominal pressure (IAP) and the vaginal biomechanical properties. Methods: A 3-dimensional computational finite element model for PF was developed based on magnetic resonance imaging from a nulliparous healthy volunteer. The model was used to simulate an IAP of 90 cm H2O and to evaluate the PF stresses in the longitudinal and transversal axes. The vaginal samples were obtained from 15 non-prolapsed female cadavers. A uniaxial tensile test to obtain stiffness and maximum stress of vaginal tissue in the longitudinal and transversal axes was performed. Results: The simulated IAP was associated with a similar PF stress state in the longitudinal and transversal axes. The stiffness and maximum stress in vaginal tissues presented a great variability between subjects. There was no difference in the vaginal tissue elasticity (6.2 ± 1.5 vs. 5.4 ± 1.1 MPa; p = 0.592) and maximum stress (2.3 ± 0.5 vs. 2.6 ± 0.9 MPa; p = 0.692) regarding the measurements in the longitudinal and transversal axes. Conclusion: The isotropic biomechanical behavior of vagina is in agreement with the PF stress state response during increased IAP.
Vaginal Flora Alterations and Clinical Symptoms in Low-Risk Pregnant Women
Authors: Gondo Fausto , da Silva Márcia G. , Polettini Jossimara , Tristao Andréa da R. , Peracoli José C. , Witkin Steven S. , Rudge Marilza V.C.
Published: April 2011

Background:To evaluate associations between alterations in vaginal flora and clinical symptoms in low-risk pregnant women. Methods:Vaginal specimens from 245 pregnant women were analyzed by microscopy for vaginal flora. Signs and symptoms of vaginal infection were determined by patient interviews and gynecologic examinations. Results:Abnormal vaginal flora was identified in 45.7% of the subjects. The final clinical diagnoses were bacterial vaginosis (21.6%), vaginal candidosis (10.2%), intermediate vaginal flora (5.2%), aerobic vaginitis (2.9%), mixed flora (2.9%) and other abnormal findings (2.9%). The percentage of women with or without clinical signs or symptoms was not significantly different between these categories. The presence of vaginal odor or vaginal discharge characteristics was not diagnostic of any specific flora alteration; pruritus was highly associated with candidosis (p < 0.0001). Compared to women with normal flora, pruritus was more prevalent in women with candidosis (p < 0.0001), while vaginal odor was associated with bacterial vaginosis (p = 0.0026). Conclusion:The prevalence of atypical vaginal flora is common in our low-risk pregnant population and is not always associated with pathology. The occurrence of specific signs or symptoms does not always discriminate between women with different types of atypical vaginal flora or between those with abnormal and normal vaginal flora.
Appendectomy in the Gynecological Setting: Intraoperative Findings and Corresponding Histopathology
Authors: Shavell Valerie I. , Mahdi Haider M. , Awonuga Awoniyi O. , Edelman David A. , Webber John D. , Gidwani Raja M. , Husain Mujtaba , Berman Jay M.
Published: April 2011

Background/Aims: To evaluate the intraoperative findings and corresponding histopathology associated with appendectomies performed during benign gynecological surgery. Methods: Retrospective case series. Results: Twenty-two appendectomies were performed from 2002 through 2008 at Hutzel Women’s Hospital due to intraoperative findings of inflammation or erythema (n = 8), periappendiceal adhesions (n = 5), injury to the appendix or mesoappendix (n = 2), fecalith (n = 2), dilation of the appendix (n = 1), adnexal mass involving the appendix (n = 1), and suspected lipoma (n = 1). Final pathology was consistent with significant findings such as acute inflammation, periappendicitis, and adhesions or endometriosis involving the appendix in 68.2% of cases. Conclusion: In the benign gynecological setting, appendectomies were primarily performed due to inflammation or erythema. In the majority of cases, significant appendiceal pathology was confirmed.
Factors Determining Conversion to Laparotomy in Patients Undergoing Total Laparoscopic Hysterectomy
Authors: Park Sung-Ho , Cho Hye-Yon , Kim Hong-Bae
Published: April 2011

Aims: To identify the risk factors determining conversion to laparotomy during total laparoscopic hysterectomy (TLH) for benign diseases. Methods: We retrospectively reviewed medical records of 288 patients that underwent TLH during the first 2 years of performing TLH at Kang-Nam Sacred Heart Hospital. Twenty-three cases were converted to laparotomy. We compared patient characteristics, indications for hysterectomy, operation time, estimated blood loss, adhesion, uterine weight and postoperative complications between failed and successful groups. Results: The rate of conversion to laparotomy was 8%. There were no differences in patient characteristics between the two groups. Independent risk factors for conversion were adhesion and uterine weight. The most common cause of the conversion to laparotomy was adhesions (p = 0.000). Uterine weight was found to be heavier in the failed group (331.5 ± 157.1 vs. 270.3 ± 132.5 g, p = 0.038). Estimated blood loss was greater in the failed group (455.6 ± 143.7 vs. 304.2 ± 45.8 ml, p = 0.047). Bladder injury occurred in the failed group more frequently than in the successful group (p = 0.024). Conclusion: An awareness of risk factors for conversion is important for better patient selection for TLH. Indirect measurement of uterine weight by sonography and detailed history taking is helpful in determining the appropriate hysterectomy route.
Beta-Fibrinogen G–455A Polymorphisms and Recurrent Miscarriage
Authors: Ticconi Carlo , Mancinelli Francesca , Gravina Paolo , Federici Giorgio , Piccione Emilio , Bernardini Sergio
Published: April 2011

Background/Aims: The aim of this study was to investigate whether differences could be detected in genotype and allele frequencies of β-fibrinogen G–455A in relation to recurrent miscarriage (RM). Methods: β-Fibrinogen G–455A polymorphism was investigated by sequencing analysis in 98 women with RM and 78 control women who had no history of miscarriage (controls). Results: The frequency of the –455 A/A genotype of β-fibrinogen was significantly different in women with RM compared with control women. The A/A genotype was found in 8 women of Group 1 (8.2%), but was not detected in any woman of the control group. In contrast, no differences were found in the allele frequencies between RM and control women. Conclusions: Women with the A/A genotype could have an increased risk of RM. However, the allele frequencies were similar between women with recurrent pregnancy loss and control women, suggesting that the effect of β-fibrinogen polymorphisms on RM, if any, is actually very slight.
Gestational Diabetes: An Evaluation of Serum Fructosamine as a Screening Test in a High-Risk Population
Authors: Agarwal Mukesh M. , Dhatt Gurdeep S. , Othman Yusra , Ljubisavljevic Milos R.
Published: April 2011

Aim: To evaluate the value of serum fructosamine as a screening test for gestational diabetes mellitus (GDM). Methods: 849 pregnant women underwent the one-step 75 g oral glucose tolerance test (OGTT) for universal screening of GDM. The fasting serum fructosamine (cFruc) was assessed using the area under the receiver operating characteristic curve (AUC). The GDM diagnostic criteria used were those of the American Diabetes Association; however, the cFruc performance was also evaluated using criteria of the World Health Organization, Australian (ADIPS), European (EASD) and International Association of Diabetes and Pregnancy Study Groups (IADPSG). Results: 113 (13.3%) women had GDM. The AUC of the cFruc was 0.60 (95% CI 0.54–0.66). A cFruc threshold of 237 µmol/l achieved an acceptable sensitivity of 85.8% (95% CI 78.0–91.0%), but the associated specificity remained poor at 23.4% (95% CI 20.0–27.0%) with a positive predictive value of just 14.7%. Overall, over 4 out of 5 pregnant women, being over this cutoff, would need the confirmatory OGTT. No cFruc threshold reached acceptable likelihood ratios to rule-in or rule-out GDM. The AUC for cFruc remained unacceptable independent of the diagnostic criteria. Conclusions: Despite all the advances in technology, serum fructosamine is a poor test to screen for GDM.
The Effect of Toremifene on Lipid Metabolism Compared with That of Tamoxifen in vitro
Authors: Sawaki Masataka , Idota Ai , Uchida Hiroki , Noda Sumiyo , Sato Shigenori , Kikumori Toyone , Imai Tsuneo
Published: April 2011

Background: Tamoxifen (TAM) and toremifene (TOR) prevent estrogen from stimulating breast cancer growth and also have agonistic effects in a number of physiological systems. TAM is known to increase intracellular triglyceride, but the action of TOR on lipid metabolism in vitro has not yet been determined. Aim: To compare the effect of TOR on lipid metabolism with that of TAM in vitro, using HepG2 cell lines. Methods: Intracellular concentrations of total cholesterol and triglyceride in HepG2 cells were measured by an enzymatic method after TAM or TOR treatment. Results: Intracellular concentrations of total cholesterol were decreased by both TAM and TOR, but not significantly different from the control level. TOR produced no changes in the intracellular concentrations of triglyceride, whereas TAM increased the intracellular concentrations of triglyceride at concentrations ranging from 10–7 to 10–5 mol/l of TAM (p < 0.05). Moreover, significant differences were noted between the two treated groups at concentrations ranging from 10–9 to 10–5 mol/l (p < 0.05). Conclusion: TOR treatment did not increase intracellular concentrations of triglyceride, although TAM treatment did so.
Digital Cytology: Current State of the Art and Prospects for the Future
Authors: Wilbur David C.
Published: April 2011

The growth of digital methods in pathology is accelerating. Digital images can be used for a variety of applications in cytology, including rapid interpretations, primary diagnosis and second opinions, continuing education and proficiency testing. All of these functions can be performed using small static digital images, real-time dynamic digital microscopy, or whole-slide images. This review will discuss the general principles of digital pathology, its methods and applications to cytologic specimens. As cytologic specimens have unique features compared to histopathology specimens, the key differences will be discussed. Technical and administrative issues in digital pathology applications and the outlook for the future of the field will be presented.
Effects of Aromatase or Estrogen Receptor Gene Deletion on Masculinization of the Principal Nucleus of the Bed Nucleus of the Stria Terminalis of Mice
Authors: Tsukahara Shinji , Tsuda Mumeko C. , Kurihara Ryohei , Kato Yukinori , Kuroda Yoshiko , Nakata Mariko , Xiao Kai , Nagata Kazuyo , Toda Katsumi , Ogawa Sonoko
Published: April 2011

The principal nucleus of the bed nucleus of the stria terminalis (BNSTp) is a sexually dimorphic nucleus, and the male BNSTp is larger and has more neurons than the female BNSTp. To assess the roles of neuroestrogen synthesized from testicular androgen by brain aromatase in masculinization of the BNSTp, we performed morphometrical analyses of the adult BNSTp in aromatase knockout (ArKO), estrogen receptor-α knockout (αERKO), and estrogen receptor-β knockout (βERKO) mice and their respective wild-type littermates. In wild-type littermates, the BNSTp of males had a larger volume and greater numbers of neuronal and glial cells than did that of females. The volume and neuron number of the BNSTp in ArKO and αERKO males and glial cell number of the BNSTp in αERKO males were significantly smaller than those of wild-type male littermates, and they were not significantly different from those in female mice with either gene knockout. In contrast, there was no significant morphological difference in the BNSTp between βERKO and wild-type mice. Next, we examined the BNSTp of ArKO males subcutaneously injected with estradiol benzoate (EB) on postnatal days 1, 2, and 3 (1.5 µg/day). EB-treated ArKO males had a significantly greater number of BNSTp neurons than did oil-treated ArKO males. The number of BNSTp neurons in EB-treated ArKO males was comparable to that in wild-type males. These findings suggested that masculinization of the BNSTp in mice involves the actions of neuroestrogen that was synthesized by aromatase and that this estrogen mostly binds to ERα during the postnatal period.
The Power of Play: Innovations in Getting Active Summit 2011
Authors: Lieberman Debra A. , Chamberlin Barbara , Medina Ernie , Franklin Barry A. , Sanner Brigid McHugh , Vafiadis Dorothea K.
Published: April 2011

Background—

To examine the influence active-play video gaming (also referred to as exergaming, exertainment, and active gaming) might have on improving health-related skills, enhancing self-esteem and self-efficacy, promoting social support, and ultimately motivating positive changes in health behaviors, the American Heart Association convened The Power of Play: Innovations in Getting Active Summit. The summit, as well as a follow-up science panel, was hosted by the American Heart Association and Nintendo of America.

Methods and Results—

The science panel discussed the current state of research on active-play video gaming and its potential to serve as a gateway experience that might motivate players to increase the amount and intensity of physical activity in their daily lives. The panel identified the need for continued research on the gateway concept and on other behavioral health outcomes that could result from active-play video games and considered how these games could potentially affect disparate populations.

Conclusions—

The summit represented an exciting first step in convening healthcare providers, behavioral researchers, and professionals from the active-play video game industry to discuss the potential health benefits of active-play video games. Research is needed to improve understanding of processes of behavior change with active games. Future games and technologies may be designed with the goal to optimize physical activity participation, increase energy expenditure, and effectively address the abilities and interests of diverse and targeted populations. The summit helped the participants gain an understanding of what is known, identified gaps in current research, and supported a dialogue for continued collaboration.