bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment for recurrence after extrapleural pneumonectomy for malignant pleural mesothelioma: A single institution experience
Authors: Okamoto Tatsuro , Yano Tokujiro , Haro Akira , Yoshida Tsukihisa , Kohno Mikihiro , Maehara Yoshihiko 
Published: April 2012

AbstractBackground:  Malignant pleural mesothelioma (MPM) is a relatively rare, aggressive neoplasm associated with asbestos exposure. Extrapleural pneumonectomy (EPP) is often performed for resectable MPM as part of a multidisciplinary treatment; however, available data on treatments for recurrence after EPP are limited.Methods:  The clinical records of consecutive MPM patients who underwent EPP at our institution from 2001 to 2010 were retrospectively reviewed. There were 10 patients who underwent EPP with or without perioperative chemotherapy; of these, recurrence was observed in eight patients.Results:  The overall median survival time and time to recurrence were 49.6 months and 15.4 months, respectively, after EPP. The first recurrence occurred within the ipsilateral thorax in four patients. These patients all underwent local treatments for their recurrence, including surgery or radiotherapy and with or without systemic chemotherapy. Other first recurrences were seen in the peritoneal space of two patients and in the contralateral lung of two patients. These patients received platinum‐based systemic chemotherapy for their recurrence. The median survival time after the first recurrence was 17.8 months, and the 2‐year survival rate was 23.4%.Conclusions:  Most patients who underwent EPP developed tumor recurrences. Direct tumor extension may be a major mechanism of recurrence. Aggressive treatment for recurrent MPM after EPP, including locoregional control and/or systemic chemotherapy, was important for achieving long‐term survival.
Aldehyde dehydrogenase 1 is associated with recurrence‐free survival but not stem cell‐like properties in hepatocellular carcinoma
Authors: Suzuki Eiichiro , Chiba Tetsuhiro , Zen Yoh , Miyagi Satoru , Tada Motohisa , Kanai Fumihiko , Imazeki Fumio , Miyazaki Masaru , Iwama Atsushi , Yokosuka Osamu 
Published: April 2012

Aim:  It has been reported that aldehyde dehydrogenase 1 A1 (ALDH1) could be not only a normal stem cell marker but also a cancer stem cell marker. ALDH1 expression could be a predictor of poor prognosis in a wide range of cancers. However, the role of ALDH1 in hepatocellular carcinoma (HCC) remains unclear.Method:  We conducted loss‐of‐function assays for ALDH1 by using short‐hairpin RNA in HCC cells and evaluated the correlation between ALDH1 expression and clinicopathological features based on immunohistochemical assessment of 49 primary HCC tissues.Results:  Neither cell proliferation nor the anchorage‐independent sphere formation ability of HCC cells were altered after ALDH1 knockdown. Flow cytometric analyses revealed that ALDH1 knockdown showed no remarkable change in the proportion of epithelial cell adhesion molecule (EpCAM)+ tumor‐initiating cells. Although non‐tumor tissues in primary HCC samples diffusely and homogenously expressed ALDH1 at low levels, tumor tissues contained cells with high levels of ALDH1 expression at varying frequencies. Primary HCC samples were categorized as ALDH1‐high or ALDH1‐low based on the percentage of ALDH1‐overexpressing cells. ALDH1‐high HCC was characterized by low serum levels of α‐fetoprotein (P < 0.01) and well‐differentiated pathology (P = 0.03). Multivariate analysis showed that high ALDH1 expression was a favorable prognostic factor in recurrence‐free survival of HCC (P = 0.02).Conclusion:  Our findings show that ALDH1 expression has little association with stem cell‐like features in HCC cells. ALDH1 might function as a differentiation marker rather than a stem cell marker in HCC.
Effect of specific activation of γ‐aminobutyric acid receptor in vivo on oxidative stress‐induced damage after extended hepatectomy
Authors: Gardner Lindsay B. , Hori Tomohide , Chen Feng , Baine Ann‐Marie T. , Hata Toshiyuki , Uemoto Shinji , Nguyen Justin H. 
Published: April 2012

Aim:  γ‐Aminobutyric acid (GABA) is a multifunctional molecule with various physiological effects throughout the body. The regulation of GABA receptor (GABAR) plays a key role in reducing the damage mediated by oxidative stress (OS). Extended hepatectomy causes fatal OS‐induced injury in the liver remnant. We aimed to investigate the effect of a GABAR agonist in extended hepatectomy.Methods:  Saline or a GABAR agonist (43.56 nmol/g bodyweight of muscimol) was administrated intravenously at 4 h preoperatively. C57BL/6 mice were divided into three groups: laparotomy only, 90% hepatectomy with saline and 90% hepatectomy with a GABAR agonist. Liver samples were obtained at 6 h after surgery.Results:  Survival curves were prolonged by the GABAR agonist. Histopathological findings and biochemical profiles showed that the GABAR agonist reduced liver damage. Immunohistological assessment demonstrated that the GABAR agonist prevented apoptotic induction. As shown by 4‐hydroxynonenal, which reflects OS‐induced damage, 90% hepatectomy caused OS and the GABAR agonist reduced OS. We measured ataxia‐telangiectasia mutated kinase (ATM), H2AX, Akt and free radical scavenging enzymes because they may be affected by GABAR regulation, and found that Akt was greatly decreased after 90% hepatectomy, but it recovered with the GABAR agonist.Conclusion:  GABAR is activated by a specific agonist in the liver in vivo. This activation reduces OS‐mediated damage after extended hepatectomy in vivo, and the mechanism via an Akt‐dependent pathway may be a key.
Carbonic Anhydrase IX Promotes Tumor Growth and NecrosisIn Vivoand Inhibition Enhances Anti-VEGF Therapy
Authors: McIntyre Alan , Patiar Shalini , Wigfield Simon , Li Ji-liang , Ledaki Ioanna , Turley Helen , Leek Russell , Snell Cameron , Gatter Kevin , Sly William S. , Vaughan-Jones Richard D. , Swietach Pawel , Harris Adrian L. 
Published: April 2012

AbstractPurpose: Bevacizumab, an anti-VEGFA antibody, inhibits the developing vasculature of tumors, but resistance is common. Antiangiogenic therapy induces hypoxia and we observed increased expression of hypoxia-regulated genes, including carbonic anhydrase IX (CAIX), in response to bevacizumab treatment in xenografts. CAIX expression correlates with poor prognosis in most tumor types and with worse outcome in bevacizumab-treated patients with metastatic colorectal cancer, malignant astrocytoma, and recurrent malignant glioma.Experimental Design: We knocked down CAIX expression by short hairpin RNA in a colon cancer (HT29) and a glioblastoma (U87) cell line which have high hypoxic induction of CAIX and overexpressed CAIX in HCT116 cells which has low CAIX. We investigated the effect on growth rate in three-dimensional (3D) culture and in vivo, and examined the effect of CAIX knockdown in combination with bevacizumab.Results: CAIX expression was associated with increased growth rate in spheroids and in vivo. Surprisingly, CAIX expression was associated with increased necrosis and apoptosis in vivo and in vitro. We found that acidity inhibits CAIX activity over the pH range found in tumors (pK = 6.84), and this may be the mechanism whereby excess acid self-limits the build-up of extracellular acid. Expression of another hypoxia inducible CA isoform, CAXII, was upregulated in 3D but not two-dimensional culture in response to CAIX knockdown. CAIX knockdown enhanced the effect of bevacizumab treatment, reducing tumor growth rate in vivo.Conclusion: This work provides evidence that inhibition of the hypoxic adaptation to antiangiogenic therapy enhances bevacizumab treatment and highlights the value of developing small molecules or antibodies which inhibit CAIX for combination therapy. Clin Cancer Res; 18(11); 3100–11. ©2012 AACR.
A Leukocyte-Mimetic Magnetic Resonance Imaging Contrast Agent Homes Rapidly to Activated Endothelium and Tracks With Atherosclerotic Lesion Macrophage Content
Authors: McAteer Martina A. , Mankia Kulveer , Ruparelia Neil , Jefferson Andrew , Nugent Hannah B. , Stork Lee-Anne , Channon Keith M. , Schneider Jurgen E. , Choudhury Robin P. 
Published: April 2012

Objective—
Endothelial cell activation is an important mediator of monocyte recruitment to sites of vascular inflammation. We hypothesized that high-affinity dual-ligand microparticles of iron oxide (MPIO), targeted to P-selectin and vascular cell adhesion molecule-1 (PV-MPIO), would identify activated endothelial cells during atherosclerosis progression.

Methods and Results—

In vivo magnetic resonance imaging in apolipoprotein E-deficient mice showed rapid binding of PV-MPIO to the aortic root, which was maximal 30 minutes post-MPIO injection and maintained at 60 minutes. Minimal binding was observed for control IgG-MPIO. Intensely low magnetic resonance signal areas, corresponding to PV-MPIO binding, were detected early (14 weeks), during foam cell formation. Contrast effects increased at 20 weeks during fibrofatty lesion development (
P
<0.05), but reduced by 30 weeks (
P
<0.01). Across all lesion severities, magnetic resonance imaging contrast effects correlated with lesion macrophage area quantified by immunohistochemistry (
R
=0.53;
P
<0.01). Near-infrared fluorescently labeled PV-MPIO were shown, by flow cytometry, to bind only activated endothelial cells and not to macrophages. Using
en face
immunofluorescence, we further demonstrate selective PV-MPIO accumulation at atherosclerosis-susceptible sites, with minimal binding to atherosclerosis-spared regions.

Conclusion—
This high-affinity leukocyte-mimetic magnetic resonance imaging agent reveals endothelial activation. PV-MPIO demonstrate exceptionally rapid in vivo steady state accumulation, providing conspicuous magnetic resonance contrast effects that can be objectively quantified. In atherosclerosis progression, PV-MPIO tracked closely with the burden and distribution of plaque macrophages, not merely plaque size. On a biocompatible platform, this approach has potential for quantitative magnetic resonance imaging of inflammatory disease activity.
Red Blood Cells Play a Role in Reverse Cholesterol Transport
Authors: Hung Kimberly T. , Berisha Stela Z. , Ritchey Brian M. , Santore Jennifer , Smith Jonathan D. 
Published: April 2012

Objective—
Reverse cholesterol transport (RCT) involves the removal of cholesterol from peripheral tissue for excretion in the feces. Here, we determined whether red blood cells (RBCs) can contribute to RCT.

Methods and Results—

We performed a series of studies in apolipoprotein AI-deficient mice where the high-density lipoprotein–mediated pathway of RCT is greatly diminished. RBCs carried a higher fraction of whole blood cholesterol than plasma in apolipoprotein AI-deficient mice, and as least as much of the labeled cholesterol derived from injected foam cells appeared in RBCs compared with plasma. To determine whether RBCs mediate RCT to the fecal compartment, we measured RCT in anemic and control apolipoprotein AI-deficient mice and found that anemia decreased RCT to the feces by over 35% after correcting for fecal mass. Transfusion of [
3
H]cholesterol-labeled RBCs led to robust delivery of the labeled cholesterol to the feces in apolipoprotein AI-deficient hosts. In wild-type mice, the majority of the blood cholesterol mass, as well as [
3
H]cholesterol derived from the injected foam cells, was found in plasma, and anemia did not significantly alter RCT to the feces after correction for fecal mass.

Conclusions—
The RBC cholesterol pool is dynamic and facilitates RCT of peripheral cholesterol to the feces, particularly in the low high-density lipoprotein state.
High Prevalence of Respiratory Ciliary Dysfunction in Congenital Heart Disease Patients With Heterotaxy
Authors: Nakhleh Nader , Francis Richard , Giese Rachel A. , Tian Xin , Li You , Zariwala Maimoona A. , Yagi Hisato , Khalifa Omar , Kureshi Safina , Chatterjee Bishwanath , Sabol Steven L. , Swisher Matthew , Connelly Patricia S. , Daniels Mathew P. , Srinivasan Ashok , Kuehl Karen , Kravitz Nadav , Burns Kimberlie , Sami Iman , Omran Heymut , Barmada Michael , Olivier Kenneth , Chawla Kunal K. , Leigh Margaret , Jonas Richard , Knowles Michael , Leatherbury Linda , Lo Cecilia W. 
Published: April 2012

Background—
Patients with congenital heart disease (CHD) and heterotaxy show high postsurgical morbidity/mortality, with some developing respiratory complications. Although this finding is often attributed to the CHD, airway clearance and left-right patterning both require motile cilia function. Thus, airway ciliary dysfunction (CD) similar to that of primary ciliary dyskinesia (PCD) may contribute to increased respiratory complications in heterotaxy patients.

Methods and Results—

We assessed 43 CHD patients with heterotaxy for airway CD. Videomicrocopy was used to examine ciliary motion in nasal tissue, and nasal nitric oxide (nNO) was measured; nNO level is typically low with PCD. Eighteen patients exhibited CD characterized by abnormal ciliary motion and nNO levels below or near the PCD cutoff values. Patients with CD aged >6 years show increased respiratory symptoms similar to those seen in PCD. Sequencing of all 14 known PCD genes in 13 heterotaxy patients with CD, 12 without CD, 10 PCD disease controls, and 13 healthy controls yielded 0.769, 0.417, 1.0, and 0.077 novel variants per patient, respectively. One heterotaxy patient with CD had the PCD causing
DNAI1
founder mutation. Another with hyperkinetic ciliary beat had 2 mutations in
DNAH11
, the only PCD gene known to cause hyperkinetic beat. Among PCD patients, 2 had known PCD causing
CCDC39
and
CCDC40
mutations.

Conclusions—
Our studies show that CHD patients with heterotaxy have substantial risk for CD and increased respiratory disease. Heterotaxy patients with CD were enriched for mutations in PCD genes. Future studies are needed to assess the potential benefit of prescreening and prophylactically treating heterotaxy patients for CD.
Simultaneous Tonsillectomy and Nasal Surgery in Adult Obstructive Sleep Apnea
Authors: Stow Nicholas W. , Sale Phillip J. P. , Lee Donald , Joffe David , Gallagher Richard M. 
Published: April 2012

ObjectiveAlthough adenotonsillectomy is the accepted treatment for obstructive sleep apnea (OSA) in the pediatric population, tonsillectomy has not been widely adopted in adults, and its success in this group has not been well reported. Despite the lack of current evidence, there may be an important role for tonsillectomy in selected adult cases, and further study is required. This is a pilot study from a larger group of subjects currently enrolled and awaiting surgery and repeat polysomnography.Study DesignRetrospective series with chart review.SettingTertiary referral teaching hospitals.Subjects and MethodsThirteen consecutive eligible subjects with tonsillar hypertrophy and OSA were identified after treatment. These patients had undergone pre‐ and postoperative polysomnography for assessment of the severity of sleep‐disordered breathing. Post hoc analysis of key parameters was performed by Wilcoxon signed rank and paired t tests. Tonsillectomy was performed on all subjects, using the diathermy dissection technique. Nasal surgery was performed simultaneously in 11 subjects for symptomatic nasal blockage unresponsive to medical treatment.ResultsThere was a statistically significant improvement in the severity of OSA after surgery. The total Respiratory Disturbance Index (RDI) was significantly decreased from median values of 31.7 to 5.5 (P =. 0002). The RDI in rapid eye movement and non–rapid eye movement sleep and the arousal index were also significantly decreased.ConclusionIn selected adult subjects, tonsillectomy with intercurrent nasal surgery should be considered an effective treatment for OSA and may reduce the requirement for continuous positive airway pressure, oral appliances, or further therapeutic intervention.
Effects of peripheral sensory nerve stimulation plus task-oriented training on upper extremity function in patients with subacute stroke: a pilot randomized crossover trial
Authors: Ikuno Koki , Kawaguchi Saori , Kitabeppu Shinsuke , Kitaura Masaki , Tokuhisa Kentaro , Morimoto Shigeru , Matsuo Atsushi , Shomoto Koji 
Published: April 2012

Objective: To investigate the feasibility of peripheral sensory nerve stimulation combined with task-oriented training in patients with stroke during inpatient rehabilitation. Design: A pilot randomized crossover trial. Setting: Two rehabilitation hospitals. Subjects: Twenty-two patients with subacute stroke. Interventions: Participants were randomly assigned to two groups and underwent two weeks of training in addition to conventional inpatient rehabilitation. The immediate group underwent peripheral sensory nerve stimulation combined with task-oriented training in the first week, followed by another week with task-oriented training alone. The delayed group underwent the same training in reverse order. Main measures: Outcome measures were the level of fatigue and Wolf Motor Function Test. Patients were assessed at baseline, one and two weeks. Results: All participants completed the study with no adverse events. There was no significant difference in level of fatigue between each treatment. From baseline to one week, the immediate group showed larger improvements than the delayed groups in the Wolf Motor Function Test (decrease in mean time (± SD) from 41.9 ± 16.2 seconds to 30.6 ± 11.4 seconds versus from 46.8 ± 19.4 seconds to 42.9 ± 14.7 seconds, respectively) but the difference did not reach significance after Bonferroni correction ( P = 0.041). Within-group comparison showed significant improvements in the Wolf Motor Function Test mean time after the peripheral sensory nerve stimulation combined with task-oriented training periods in each group ( P < 0.01). Conclusion: Peripheral sensory nerve stimulation is feasible in clinical settings and may enhance the effects of task-oriented training in patients with subacute stroke.
Cement dust pollution induces toxicity or deficiency of some essential elements in wild plants growing around a cement factory
Authors: Mutlu Salih , Atici Ökkeş , Gülen Yasir 
Published: April 2012

In the present study, it was aimed to determine the effects of cement dust pollution on contents of some significant essential elements (P, S, K, Ca, Fe and Cl) in wild plants ( Medigago varia, Anchusa leptophylla, Euphorbia orientalis, Lactuca serriola, Artemisia spicigera, Crambe orientalis, Convolvulus sepium and Senecio vernalis) using wavelength-dispersive spectrometer X-ray fluorescence technique. Plant samples were collected from different locations around a cement factory which is located at Askale about 50 km from Erzurum (Turkey). The element contents in the plant specimens that existed in both 0–100 m (dense dusted) and 2000 m (undusted) areas were compared. P, S, K and Cl contents were found to be high in the plants growing in areas 0–100 m from the cement factory, compared to same plants at 2000 m far from the factory. However, Ca and Fe contents were determined to be low in plants growing in 0–100 m area from the factory. Results of the study can contribute to understand how mineral deficiency and toxicity lead to detrimental effects on plant growth and development in the fields contaminated by cement dust.
Temporal Changes in Collagen Cross-Links in Spontaneous Articular Cartilage Repair
Authors: Terajima Masahiko , Damle Sheela , Penmatsa Madhuri , West Paul , Bostrom Mathias , Hidaka Chisa , Yamauchi Mitsuo , Pleshko Nancy 
Published: April 2012

Objective: Little is known about how the biochemical properties of collagen change during tissue regeneration following cartilage damage. In the current study, temporal changes in cartilage repair tissue biochemistry were assessed in a rabbit osteochondral defect. Design: Bilateral full-thickness 3-mm osteochondral trochlear groove defects were created in 54 adult male skeletally mature New Zealand white rabbits, and tissue repair was monitored over 16 weeks. Collagen content, cross-links, lysyl hydroxylation, gene expression, histological grading, and Fourier transform infrared analyses were performed at 2, 4, 6, 8, 12, and 16 weeks. Results: Defect fill occurred at ~4 weeks postinjury; however, histological grading showed that the repair tissue never became normal, primarily due to the presence of fibrocartilage. Gene expression levels of Col1a1 and Col IIaI were higher in the defect compared with adjacent regions. Collagen content in the repair tissue reached the level of normal cartilage at 6 weeks, but it took 12 weeks for the extent of lysine hydroxylation to return to normal. Divalent immature cross-links markedly increased in the early stages of repair. Though the levels gradually diminished thereafter, they never returned to the normal levels. The mature cross-link, pyridinoline, gradually increased with time and nearly reached normal levels by week 16. Infrared imaging data of protein content paralleled the biochemical data. However, collagen maturity, a parameter previously shown to reflect collagen cross-link ratios in bone, did not correlate with the biochemical determination of cross-links in the repair tissue. Conclusion: Collagen biochemical data could provide markers for clinical monitoring in a healing defect.
Extracardiac Fontan With Direct Cavopulmonary Connections: Midterm Results
Authors: Liu Jinfen , Hong Haifa , Zhu Zhongqun , Lu Yanan , Chen Huiwen 
Published: April 2012

Background: The aim of this study was to analyze the midterm results following direct superior and inferior cavopulmonary connections (DCPC) to create Fontan circulation in patients with functionally univentricular hearts. Methods: Retrospective review of patients operated between January 2005 and May 2011. Results: The 25 consecutive patients who underwent this type of operation were retrospectively reviewed. There were 15 (60%) males and ten (40%) females, with median age of 73 months (range: 16-150 months) and median weight of 25 kg (range: 11-46 kg). Aortic cross-clamping used in ten patients, with median cross-clamp time of 40 minutes (range: 23-99) and median cardiopulmonary bypass (CPB) time of 135 minutes (range: 76-179 minutes). The remaining 15 patients were operated without aortic cross-clamping. Their median CPB time was 112 minutes (range: 82-139 minutes). Fenestration was performed in 15 cases. Associated intracardiac procedures were performed on ten patients. The follow-up period ranged from two months to six years. Operative mortality and late mortality after discharge were zero. Major postoperative complications included supraventricular tachycardia in one patient, oliguria and peritoneal dialysis in one patient, chest drainage persisting more than seven days in five patients (20%). One patient developed sinus bradycardia in association with sinus pauses two months after discharge. One patient developed pericardial effusion one month after discharge. Conclusions: Direct superior and inferior cavopulmonary connections to create Fontan circulation in appropriately selected patients with functionally univentricular hearts can be performed with low risk and a low rate of reintervention. The midterm results are favorable.