bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of resistance to high and low linear energy transfer radiation in myeloid leukemia cells
Authors: Haro Kurtis J. , Scott Andrew C. , Scheinberg David A. 
Published: July 2012

Abstract
Low linear energy transfer (LET) ionizing radiation (IR) is an important form of therapy for acute leukemias administered externally or as radioimmunotherapy. IR is also a potential source of DNA damage. High LET IR produces structurally different forms of DNA damage and has emerged as potential treatment of metastatic and hematopoietic malignancies. Therefore, understanding mechanisms of resistance is valuable. We created stable myeloid leukemia HL60 cell clones radioresistant to either γ-rays or α-particles to understand possible mechanisms in radioresistance. Cross-resistance to each type of IR was observed, but resistance to clustered, complex α-particle damage was substantially lower than to equivalent doses of γ-rays. The resistant phenotype was driven by changes in: apoptosis; late G2/M checkpoint accumulation that was indicative of increased genomic instability; stronger dependence on homology-directed repair; and more robust repair of DNA double-strand breaks and sublethal-type damage induced by γ-rays, but not by α-particles. The more potent cytotoxicity of α-particles warrants their continued investigation as therapies for leukemia and other cancers.
The pathway of cell dismantling during programmed cell death in lace plant (Aponogeton madagascariensis) leaves
Authors: Wertman Jaime , Lord Christina EN , Dauphinee Adrian N , Gunawardena Arunika HLAN 
Published: July 2012

Abstract

Background
Developmentally regulated programmed cell death (PCD) is the controlled death of cells that occurs throughout the life cycle of both plants and animals. The lace plant (Aponogeton madagascariensis) forms perforations between longitudinal and transverse veins in spaces known as areoles, via developmental PCD; cell death begins in the center of these areoles and develops towards the margin, creating a gradient of PCD. This gradient was examined using both long- and short-term live cell imaging, in addition to histochemical staining, in order to establish the order of cellular events that occur during PCD.

Results
The first visible change observed was the reduction in anthocyanin pigmentation, followed by initial chloroplast changes and the bundling of actin microfilaments. At this stage, an increased number of transvacuolar strands (TVS) was evident. Perhaps concurrently with this, increased numbers of vesicles, small mitochondrial aggregates, and perinuclear accumulation of both chloroplasts and mitochondria were observed. The invagination of the tonoplast membrane and the presence of vesicles, both containing organelle materials, suggested evidence for both micro- and macro-autophagy, respectively. Mitochondrial aggregates, as well as individual chloroplasts were subsequently seen undergoing Brownian motion in the vacuole. Following these changes, fragmentation of nuclear DNA, breakdown of actin microfilaments and early cell wall changes were detected. The vacuole then swelled, causing nuclear displacement towards the plasma membrane (PM) and tonoplast rupture followed closely, indicating mega-autophagy. Subsequent to tonoplast rupture, cessation of Brownian motion occurred, as well as the loss of mitochondrial membrane potential (ΔΨm), nuclear shrinkage and PM collapse. Timing from tonoplast rupture to PM collapse was approximately 20 minutes. The entire process from initial chlorophyll reduction to PM collapse took approximately 48 hours. Approximately six hours following PM collapse, cell wall disappearance began and was nearly complete within 24 hours.

Conclusion
Results showed that a consistent sequence of events occurred during the remodelling of lace plant leaves, which provides an excellent system to study developmental PCD in vivo. These findings can be used to compare and contrast with other developmental PCD examples in plants.
Left ventricular hypertrabeculation/noncompaction with epilepsy, other heart defects, minor facial anomalies and new copy number variants
Authors: Nagel Bert , Gruber-Sedlmayr Ursula , Uhrig Sabine , Stöllberger Claudia , Klopocki Eva , Finsterer Josef 
Published: July 2012

Abstract

Background
Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality of unknown etiology which has been described in children as well as in adults with and without chromosomal aberrations. LVHT has been reported in association with various cardiac and extracardiac abnormalities like epilepsy and facial dysmorphism.

Case presentation
A unique combination of LVHT, atrial septal defect, pulmonary valve stenosis, aortic stenosis, epilepsy and minor facial anomalies is presented in a 5.5 years old girl. Microarray-based genomic hybridization (array-CGH) detected six previously not described copy number variants (CNVs) inherited from a clinically unaffected father and minimally affected mother, thus, most likely, not clinically significant but rare benign variants.

Conclusions
Despite this complex phenotype de novo microdeletions or microduplications were not detected by array CGH. Further investigations, such as whole exome sequencing, could reveal point mutations and small indels as the possible cause.
Intraneural metastasis of gastric carcinoma leads to sciatic nerve palsy
Authors: Ichikawa Jiro , Matsumoto Seiichi , Shimoji Takashi , Tanizawa Taisuke , Gokita Tabu , Hayakawa Keiko , Aoki Kaoru , Ina Saori , Kanda Hiroaki 
Published: July 2012

AbstractBackgroundSoft tissue metastases, in particular intraneural metastasis, from any carcinomas seldom occur. To our knowledge, no case of sciatic nerve palsy due to intraneural metastasis of gastric carcinoma is reported in the literature.Case presentationA case is reported of a 82-year old woman with sciatic nerve palsy with intraneural metastasis of gastric carcinoma. Although she had undergone partial gastrectomy with T2b, N0, M0 two years ago and primary site was cured, she developed sciatic nerve palsy from the carcinoma metastasis directly to the nerve. Operative resection and Histological examination revealed poorly differentiated adenocarcinoma, the same as her primary site adenocarcinoma.ConclusionsSciatica is usually caused by a herniated disc or spinal canal stenosis. Sciatic nerve palsy may be caused by nondiscogenic etiologies that may be either intrapelvic or extrapelvic. It is important to image the entire course of the nerve to distinguish these etiologies quickly. The longer the nerve compression the less likely a palsy will recover. Surgery is a good intervention that simultaneously obtains a tissue diagnosis and decompresses the nerve.
Budget impact analysis of ustekinumab in the management of moderate to severe psoriasis in Greece
Authors: Avgerinou Georgia , Bassukas Ioannis , Chaidemenos Georgios , Katsampas Andreas , Kosmadaki Marita , Kousoulakou Hara , Petridis Athanasios , Schenkel Brad , Sotiriadis Dimitrios , Spiliopoulos Theofanis , Stavropoulos Panagiotis , Toumpi Evgenia , Xaplanteris Loukas 
Published: July 2012

Abstract

Background
The purpose of this study was to estimate the annual and per-patient budget impact of the treatment of moderate to severe psoriasis in Greece before and after the introduction of ustekinumab.

Methods
A budget impact model was constructed from a national health system perspective to depict the clinical and economic aspects of psoriasis treatment over 5 years. The model included drug acquisition, monitoring, and administration costs for both the induction and maintenance years for patients in a treatment mix with etanercept, adalimumab, infliximab, with or without ustekinumab. It also considered the resource utilization for non-responders. Greek treatment patterns and resource utilization data were derived from 110 interviews with dermatologists conducted in February 2009 and evaluated by an expert panel of 18 key opinion leaders. Officially published sources were used to derive the unit costs. Costs of adverse events and indirect costs were excluded from the analysis. Treatment response was defined as the probability of achieving a PASI 50, PASI 75, or PASI 90 response, based on published clinical trial data.

Results
The inclusion of ustekinumab in the biological treatment mix for moderate to severe psoriasis is predicted to lead to total per-patient savings of €443 and €900 in years 1 and 5 of its introduction, respectively. The cost savings were attributed to reduced administration costs, reduced hospitalizations for non-responders, and improved efficacy. These results were mainly driven by the low number of administrations required with ustekinumab over a 5 year treatment period (22 for ustekinumab, compared with 272 for etanercept, 131 for adalimumab, and 36 for infliximab).

Conclusions
The inclusion of ustekinumab in the treatment of moderate to severe psoriasis in Greece is anticipated to have short- and long-term health and economic benefits, both on an annual and per-patient basis.
A stepwise approach for the reproducible optimization of PAMO expression in Escherichia coli for whole-cell biocatalysis
Authors: van Bloois Edwin , Dudek Hanna M , Duetz Wouter A , Fraaije Marco W 
Published: July 2012

Abstract

Background
Baeyer-Villiger monooxygenases (BVMOs) represent a group of enzymes of considerable biotechnological relevance as illustrated by their growing use as biocatalyst in a variety of synthetic applications. However, due to their increased use the reproducible expression of BVMOs and other biotechnologically relevant enzymes has become a pressing matter while knowledge about the factors governing their reproducible expression is scattered.

Results
Here, we have used phenylacetone monooxygenase (PAMO) from Thermobifida fusca, a prototype Type I BVMO, as a model enzyme to develop a stepwise strategy to optimize the biotransformation performance of recombinant E. coli expressing PAMO in 96-well microtiter plates in a reproducible fashion. Using this system, the best expression conditions of PAMO were investigated first, including different host strains, temperature as well as time and induction period for PAMO expression. This optimized system was used next to improve biotransformation conditions, the PAMO-catalyzed conversion of phenylacetone, by evaluating the best electron donor, substrate concentration, and the temperature and length of biotransformation. Combining all optimized parameters resulted in a more than four-fold enhancement of the biocatalytic performance and, importantly, this was highly reproducible as indicated by the relative standard deviation of 1% for non-washed cells and 3% for washed cells. Furthermore, the optimized procedure was successfully adapted for activity-based mutant screening.

Conclusions
Our optimized procedure, which provides a comprehensive overview of the key factors influencing the reproducible expression and performance of a biocatalyst, is expected to form a rational basis for the optimization of miniaturized biotransformations and for the design of novel activity-based screening procedures suitable for BVMOs and other NAD(P)H-dependent enzymes as well.
Superior semicircular canal dehiscence in East Asian women with osteoporosis
Authors: Yu Alexander , Teich Douglas L , Moonis Gul , Wong Eric T 
Published: July 2012

Abstract

Background
Superior semicircular canal dehiscence (SSCD) may cause Tullio phenomenon (sound-induced vertigo) or Hennebert sign (valsalva-induced vertigo) due to the absence of bone overlying the SSC. We document a case series of elderly East Asian women with atypical SSCD symptoms, radiologically confirmed dehiscence and concurrent osteoporosis.

Methods
A retrospective record review was performed on patients with dizziness, vertigo, and/or imbalance from a neurology clinic in a community health center serving the East Asian population in Boston. SSCD was confirmed by multi-detector, high-resolution CT of the temporal bone (with Pöschl and Stenvers reformations) and osteoporosis was documented by bone mineral density (BMD) scans.

Results
Of the 496 patients seen in the neurology clinic of a community health center from 2008 to 2010, 76 (17.3%) had symptoms of dizziness, vertigo, and/or imbalance. Five (6.6%) had confirmed SSCD by multi-detector, high-resolution CT of the temporal bone with longitudinal areas of dehiscence along the long axis of SSC, ranging from 0.4 to 3.0 mm, as seen on the Pöschl view. Two of the 5 patients experienced motion-induced vertigo, two fell due to disequilibrium, and one had chronic dizziness. None had a history of head trauma, otologic surgery, or active intracerebral disease. On neurological examination, two patients had inducible vertigo on Dix-Hallpike maneuver and none experienced cerebellar deficit, Tullio phenomenon, or Hennebert sign. All had documented osteoporosis or osteopenia by BMD scans. Three of them had definite osteoporosis, with T-scores < −2.5 in the axial spine, while another had osteopenia with a T-score of −2.3 in the left femur.

Conclusions
We describe an unusual presentation of SSCD without Tullio phenomenon or Hennebert sign in a population of elderly, East Asian women. There may be an association of SSCD and osteoporosis in this population. Further research is needed to determine the incidence and prevalence of this disorder, as well as the relationship of age, race, osteoporosis risk, and the development of SSCD.
Development of one-step TaqMan® real-time reverse transcription-PCR and conventional reverse transcription-PCR assays for the detection of equine rhinitis A and B viruses
Authors: Lu Zhengchun , Timoney Peter J , White Jena , Balasuriya Udeni BR 
Published: July 2012

Abstract

Background
Equine rhinitis viruses A and B (ERAV and ERBV) are common equine respiratory viruses belonging to the family Picornaviridae. Sero-surveillance studies have shown that these two viral infections are prevalent in many countries. Currently, the diagnosis of ERAV and ERBV infections in horses is mainly based on virus isolation (VI). However, the sensitivity of VI testing varies between laboratories due to inefficient viral growth in cell culture and lack of cytopathic effect. Therefore, the objective of this study was to develop molecular diagnostic assays (real-time RT-PCR [rRT-PCR] and conventional RT-PCR [cRT-PCR] assays) to detect and distinguish ERAV from ERBV without the inherent problems traditionally associated with laboratory diagnosis of these infections.

Results
Three rRT-PCR assays targeting the 5'-UTR of ERAV and ERBV were developed. One assay was specific for ERAV, with the two remaining assays specific for ERBV. Additionally, six cRT-PCR assays targeting the 5'-UTR and 3D polymerase regions of ERAV and ERBV were developed. Both rRT-PCR and cRT-PCR assays were evaluated using RNA extracted from 21 archived tissue culture fluid (TCF) samples previously confirmed to be positive for ERAV (n = 11) or ERBV (n = 10) with mono-specific rabbit antisera. The ERAV rRT-PCR and cRT-PCR assays could only detect ERAV isolates and not ERBV isolates. Similarly, the ERBV rRT-PCR and cRT-PCR assays could only detect ERBV isolates and not ERAV isolates. None of the rRT-PCR or cRT-PCR assays cross-reacted with any of the other common equine respiratory viruses. With the exception of one cRT-PCR assay, the detection limit of all of these assays was 1 plaque forming unit per ml (pfu/ml).

Conclusion
The newly developed rRT-PCR and cRT-PCR assays provide improved diagnostic capability for the detection and differentiation of ERAV and ERBV. However, a larger number of clinical specimens will need to be tested before each assay is adequately validated for the detection of ERAV and/or ERBV in suspect cases of either viral infection.
Luminal A and luminal B (HER2 negative) subtypes of breast cancer consist of a mixture of tumors with different genotype
Authors: Yanagawa Masumi , Ikemot Kenzo , Kawauchi Shigeto , Furuya Tomoko , Yamamoto Shigeru , Oka Masaaki , Oga Atunori , Nagashima Yukiko , Sasaki Kohsuke 
Published: July 2012

Abstract

Background
The St Gallen International Expert Consensus 2011 has proposed a new classification system for breast cancer. The purpose of this study was to elucidate the relationship between the breast cancer subtypes determined by the new classification system and genomic characteristics.

Methods
Invasive breast cancers (n = 363) were immunohistochemically classified as follows: 111 (30.6%) as luminal A, 95 (26.2%) as luminal B (HER2 negative), 69 (19.0%) as luminal B (HER2 positive), 41 (11.3%) as HER2, and 47 (12.9%) as basal-like subtypes.

Results
The high expression of Ki-67 antigen was detected in 236 tumors; no cases of luminal A subtype showed high expression of the Ki-67 antigen, but more than 85% of tumors of the other subtypes showed high expression. In addition, DNA ploidy and chromosomal instability (CIN) were assessed using imaging cytometry and FISH, respectively. In this series, 336 (92.6%) tumors consisted of 129 diploid/CIN- and 207 aneuploid/CIN + tumors. Diploid/CIN- and aneuploid/CIN+ features were detected in 64.9% and 27.9% of luminal A, 41.1% and 49.5% of luminal B (HER2-), 11.6% and 81.2% of luminal B (HER2+), 4.9% and 90.2% of HER2, and 17.0% and 76.6% of basal-like subtypes, respectively. Unlike the luminal B (HER2+), HER2 and basal-like subtypes, the luminal A and luminal B (HER2-) subtypes were heterogeneous in terms of DNA ploidy and CIN.

Conclusions
It is reasonable to propose that the luminal A and luminal B (HER2-) subtypes should be further divided into two subgroups, diploid/CIN- and aneuploid/CIN+, based on their underlying genomic status.
Comparison of seasonal variation in the fasting respiratory quotient of young Japanese, Polish and Thai women in relation to seasonal change in their percent body fat
Authors: Morinaka Tomoko , Wozniewicz Malgorzata , Jeszka Jan , Bajerska Joanna , Limtrakul Porn-ngarm , Makonkawkeyoon Luksana , Hirota Naoko , Kumagai Shoko , Sone Yoshiaki 
Published: July 2012

Abstract

Background
From the viewpoint of human physiological adaptability, we previously investigated seasonal variation in the amount of unabsorbed dietary carbohydrates from the intestine after breakfast in Japanese, Polish and Thai participants. In this investigation we found that there were significant seasonal variations in the amount of unabsorbed dietary carbohydrates in Japanese and Polish participants, while we could not find significant seasonal variation in Thai participants. These facts prompted us to examine seasonal variations in the respiratory quotient after an overnight fast (an indicator of the ratio of carbohydrate and fat oxidized after the last meal) with female university students living in Osaka (Japan), Poznan (Poland) and Chiang Mai (Thailand).

Methods
We enrolled 30, 33 and 32 paid participants in Japan, Poland and Thailand, respectively, and measurements were taken over the course of one full year. Fasting respiratory quotient was measured with the participants in their postabsorptive state (after 12 hours or more fasting before respiratory quotient measurement). Respiratory quotient measurements were carried out by means of indirect calorimetry using the mixing chamber method. The percent body fat was measured using an electric bioelectrical impedance analysis scale. Food intake of the participants in Osaka and Poznan were carried out by the Food Frequency Questionnaire method.

Results
There were different seasonal variations in the fasting respiratory quotient values in the three different populations; with a significant seasonal variation in the fasting respiratory quotient values in Japanese participants, while those in Polish and Thai participants were non-significant. We found that there were significant seasonal changes in the percent body fat in the three populations but we could not find any significant correlation between the fasting respiratory quotient values and the percent body fat.

Conclusions
There were different seasonal variations in the fasting respiratory quotient values in the three different populations. There were significant seasonal changes in the percent body fat in the three populations but no significant correlation between the fasting respiratory quotient values and the percent body fat.
Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer
Authors: Kim Jisun , Han Wonshik , Moon Hyeong-Gon , Ahn Soo Kyung , Shin Hee-Chul , You Jee-Man , Han Sae-Won , Im Seock-Ah , Kim Tae-You , Koo Hye Ryoung , Chang Jung Min , Cho Nariya , Moon Woo Kyung , Noh Dong-Young 
Published: July 2012

Abstract
Introduction
Anti-estrogen therapy has been shown to reduce mammographic breast density (MD). We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting response to adjuvant endocrine therapy (ET) in breast cancer.

Methods
We analyzed data for 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET, including tamoxifen and aromatase inhibitors. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction (MDR) was defined as the absolute difference in MD of mammograms taken preoperatively and 8-20 months after the start of ET.

Results
At a median follow-up of 68.8 months, the overall breast cancer recurrence rate was 7.5% (80/1065). Mean MDR was 5.9% (range, -17.2% to 36.9%). Logistic regression analysis showed that age < 50 years, high preoperative MD, and long interval between start of ET to follow-up mammogram were significantly associated with larger MDR (p < 0.05). In a survival analysis, tumor size, lymph node positivity, high Ki-67 (≥ 10%), and low MDR were independent factors significantly associated with recurrence-free survival (p < 0.05). Compared with the group showing the greatest MDR (≥ 10%), the hazard ratios for MDRs of 5-10%, 0-5%, and < 0% were 1.33, 1.92, and 2.26, respectively.

Conclusions
MD change during short-term use of adjuvant ET was a significant predictor of long-term recurrence in women with ER-positive breast cancer. Effective treatment strategies are urgently needed in patients with low MDR despite about 1 year of ET.
Short-range homing in a site-specific fish: search and directed movements
Authors: Mitamura Hiromichi , Uchida Keiichi , Miyamoto Yoshinori , Kakihara Toshiharu , Miyagi Aki , Kawabata Yuuki , Ichikawa Kotaro , Arai Nobuaki 
Published: July 2012

SUMMARY
Sedentary and territorial rockfish of the genus Sebastes exhibit distinctive homing ability and can travel back to an original location after displacements of metres or even kilometres. However, little is known about the behavioural and sensory mechanisms involved in homing. Although our previous study demonstrated that nocturnal black rockfish Sebastes cheni predominantly use their olfactory sense for homing from an unfamiliar area, the possibility of using landmarks in a familiar area cannot be discounted; i.e. site-specific fish are likely to use three-dimensional spatial memory for navigation and orientation. Using high-resolution acoustic telemetry, we investigated whether S. cheni exhibit distinctive homing paths. Results show that all of the eight rockfish increased their effort within a small area of an unfamiliar region around the release site just after displacement, suggesting that the rockfish probably searched for the homeward direction. The rockfish showed the search movement in the upstream and/or downstream direction, which did not lead home. Finally, after returning to their familiar area, the rockfish exhibited more directed movements with faster speeds at a shallower depth, which was similar to the depth utilised in daily life as well as that of the fish capture.