bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microvascular Reactivity in Response to Smoking and Oral Antioxidants in Humans
Authors: HENRIKSSON PETER , DICZFALUSY ULF , FREYSCHUSS ANNA 
Published: August 2011

Please cite this paper as: Henriksson, Diczfalusy and Freyschuss (2012). Microvascular Reactivity in Response to Smoking and Oral Antioxidants in Humans. Microcirculation 19(1), 86–93.AbstractObjective:  To investigate whether a daily intake of a moderate dose of antioxidants modifies the microcirculatory response to smoking, assuming a major influence of oxidative stress on microcirculation.Methods:  The microvascular response to smoking was assessed in individual capillaries by capillaroscopy before and after two weeks of treatment with oral antioxidants.Results:  Smoking prolonged time to peak (TtP) capillary blood flow velocity in all subjects. When the subjects were pre‐treated with ascorbate, TtP was comparable to baseline values of untreated subjects. No significant effect of vitamin E was observed either before or after smoking. Capillary blood flow velocity increased after treatment with ascorbate as well as after vitamin E. However, significant reductions in velocity were still observed in response to smoking even after subjects consumed ascorbate and vitamin E (p < 0.0004 and p < 0.000008 respectively).Conclusions:  This study focused on individual capillaries, and confirms that smoking has a very pronounced, direct and reproducible microvascular effect possible to demonstrate in vivo in human capillaries. Moderate intake of the antioxidant ascorbate clearly mitigated the effects induced by smoking. TtP after smoking in subjects treated with ascorbate was similar to that observed in untreated subjects before smoking a cigarette. Thus, oxidative stress could be assumed to play a role in the effects of smoking on microcirculation.
Corneal nerve fiber pathology in Japanese type 1 diabetic patients and its correlation with antecedent glycemic control and blood pressure
Authors: Ishibashi Fukashi , Okino Mika , Ishibashi Marina , Kawasaki Asami , Endo Naoko , Kosaka Aiko , Uetake Harumi 
Published: August 2011

AbstractAims/Introduction:  Morphological changes to corneal C‐fibers in Japanese type 1 diabetic patients were visualized by corneal confocal microscopy (CCM). The effects of prior glycemic control and blood pressure on morphological parameters were clarified.Materials and Methods:  Corneal nerve fibers were visualized by CCM in 38 Japanese type 1 diabetic patients (14 with and 24 without neuropathy) and 38 controls. Morphological parameters were compared and related to annual mean HbA1c, blood pressure, and serum lipid levels of previous years prior to CCM examination.Results:  Compared with controls, diabetic patients had reduced corneal nerve fiber length (CNFL; 9.80 ± 0.38 vs 13.65 ± 0.88 mm/mm2; P < 0.001), reduced density (CNFD; 25.32 ± 1.04 vs 36.62 ± 2.37/mm2; P < 0.0005), lower frequency of beading (22.38 ± 0.73 vs 30.44 ± 1.03/0.1 mm; P < 0.0001), and increased tortuosity (3.13 ± 0.09 vs 1.74 ± 0.06; P < 0.0001). These changes were found in patients without neuropathy. There was no difference in nerve branches between controls and diabetic patients. The mean annual HbA1c level for the 7–10 years prior to CCM examination was an independent predictor of reduced CNFL and CNFD; HbA1c levels obtained 1–3 months and 1 year prior to CCM, as well as blood pressure 3, 5, and 6 years prior to CCM, were independent predictors of reduced beading frequency.Conclusions:  Corneal confocal microscopy is a novel, noninvasive technique to evaluate morphological changes of corneal C‐fibers in type 1 diabetes. Antecedent hyperglycemia and blood pressure have different time‐dependent effects on CNFL and CNFD and the frequency of beading. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00157.x, 2011)
Early Detection of Tumor Response by FLT/MicroPET Imaging in a C26 Murine Colon Carcinoma Solid Tumor Animal Model
Authors: Lee Wan-Chi , Chang Chih-Hsien , Ho Chung-Li , Chen Liang-Cheng , Wu Yu-Hsien , Chen Jenn-Tzong , Wang Ying-Ling , Lee Te-Wei 
Published: August 2011

Fluorine‐18 fluorodeoxyglucose ( 18F‐FDG) positron emission tomography (PET) imaging demonstrated the change of glucose consumption of tumor cells, but problems with specificity and difficulties in early detection of tumor response to chemotherapy have led to the development of new PET tracers. Fluorine‐18‐fluorothymidine ( 18F‐FLT) images cellular proliferation by entering the salvage pathway of DNA synthesis. In this study, we evaluate the early response of colon carcinoma to the chemotherapeutic drug, lipo‐Dox, in C26 murine colorectal carcinoma‐bearing mice by  18F‐FDG and  18F‐FLT. The male BALB/c mice were bilaterally inoculated with 1 × 105 and 1 × 106 C26 tumor cells per flank. Mice were intravenously treated with 10 mg/kg lipo‐Dox at day 8 after  18F‐FDG and  18F‐FLT imaging. The biodistribution of  18F‐FDG and  18F‐FLT were followed by the microPET imaging at day 9. For the quantitative measurement of microPET imaging at day 9,  18F‐FLT was superior to
18F‐FDG for early detection of tumor response to Lipo‐DOX at various tumor sizes (P < 0.05). The data of biodistribution showed similar results with those from the quantification of SUV (standard uptake value) by microPET imaging. The study indicates that  18F‐FLT/microPET is a useful imaging modality for early detection of chemotherapy in the colorectal mouse model.
Unraveling the Role of Hypoxia-Inducible Factor in Renal Cell Carcinoma: A Biological and Therapeutic Perspective
Authors: Pal Sumanta Kumar , Figlin Robert A. 
Published: August 2011

Abstract
The genetic control of hypoxia-inducible factor (HIF) has long been associated with the pathogenesis of clear cell renal cell carcinoma. Only recently have the complex genetics and biology of relevant HIF subtypes been unraveled, leading to potential novel strategies for treating this disease. Cancer Discovery; 1(3); 198–9. © 2011 AACR.
Commentary on Shen et al., p. 222.
A Shining Light in the Darkness for the Treatment of Pancreatic Neuroendocrine Tumors
Authors: Capdevila Jaume , Tabernero Josep 
Published: August 2011

Abstract
Gastroenteropancreatic neuroendocrine tumors are rare neoplasms; past decades have seen limited research channeled into this area. Recently, 2 placebo-controlled phase III trials using 2 drugs—everolimus and sunitinib—with distinct molecular rationales achieved their principal objective of increasing survival in patients with advanced pancreatic neuroendocrine tumors (PNET). Nonetheless, several questions remain unanswered, notably defining the optimal schedule for integrating these targeted agents with conventional cytotoxics and other treatment options, and identifying appropriate biomarkers for patients with the potential to derive greater benefit. In this article, we analyze the results of the 2 largest studies ever completed in patients with PNETs and discuss the challenges for future drug development in this setting.
Summary: Sunitinib and everolimus will become new treatment options for patients with PNETs and will be integrated into the complex therapeutic management of this disease. In this review, we summarize the evidence-based data of these drugs as well as the molecular-based science in this setting that will lay the groundwork for future studies. Cancer Discovery; 1(3); 213–21. © 2011 AACR.
Qualitative research in evidence-based medicine: Improving decision-making and participation in randomized controlled trials of cancer treatments
Authors: Audrey Suzanne 
Published: August 2011

Background: Since the 1990s there has been increasing emphasis on ‘evidence-based medicine’. The randomized controlled trial is widely regarded as the ‘gold-standard’ study design for evaluating interventions. However, placing too strong an emphasis on a phase III trial, to the neglect of earlier development and piloting work, may result in weaker interventions that are more difficult to evaluate and less likely to be implemented. Aim: To illustrate the benefits and outcomes of qualitative research at the early stages of the research continuum. Setting/Participants: Two cancer studies are evaluated in which the best treatment option is uncertain: ASPECTS (A Study of Patients ExperienCes of TreatmentS) and ProtecT (Prostate Testing for Cancer and Treatment). Design: To examine decision-making in relation to palliative chemotherapy for advanced cancer, ASPECTS was a qualitative study involving non-participant observation and recording of oncology consultations. During the ProtecT feasibility study, recruitment interviews were routinely audiotaped and in-depth interviews conducted with men to explore their understanding of treatment options and randomization to trial arms. Results: ASPECTS identified that insufficient information was given to patients about the survival benefits of palliative chemotherapy with implications for informed consent. ProtecT illustrated the effective use of qualitative research methods to resolve recruitment and randomization problems for a randomized controlled trial. Conclusions: These studies illustrate the value of qualitative research, particularly during the earlier phases of the research continuum. Such research may generate hypotheses, strengthen the development and implementation of interventions and enhance their evaluation: all of which are essential to evidence-based medicine.
Targeted therapy for NSCLC: ALK inhibition
Authors: Pearson Rachel , Kolesar Jill M 
Published: August 2011

Purpose: The purpose of this review article is to describe the emerging data of ALK receptor tyrosine kinaase inhibitors in ALK mutation positive NSCLC. Summary: ALK mutations have been identified in approximately 2.4–13% of patients with NSCLC, occurring more frequently in adenocarcinomas and never and light smokers. Crizotinib is an oral ATP-competitive selective inhibitor of the ALK and MET tyrosine kinases that inhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations. A phase II study demonstrated an overall response rate of 57% (95% CI, 46 to 68), with the most common toxicity grade I fatigue and visual disturbances. Elevations in lever function tests were also reported. Conclusion: The ALK receptor tyrosine kinase inhibitor crizotinib may be an effective therapy in ALK mutated NSCLC and is currently being compared to standard chemotherapy for advanced or metastatic NSCLC.
Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells
Authors: Chen Pei-Min , Yen Men-Luh , Liu Ko-Jiunn , Sytwu Huey-Kang , Yen B-Linju 
Published: August 2011

AbstractIn recent years, a large number of studies have contributed to our understanding of the immunomodulatory mechanisms used by multipotent mesenchymal stem cells (MSCs). Initially isolated from the bone marrow (BM), MSCs have been found in many tissues but the strong immunomodulatory properties are best studied in BM MSCs. The immunomodulatory effects of BM MSCs are wide, extending to T lymphocytes and dendritic cells, and are therapeutically useful for treatment of immune-related diseases including graft-versus-host disease as well as possibly autoimmune diseases. However, BM MSCs are very rare cells and require an invasive procedure for procurement. Recently, MSCs have also been found in fetal-stage embryo-proper and extra-embryonic tissues, and these human fetal MSCs (F-MSCs) have a higher proliferative profile, and are capable of multilineage differentiation as well as exert strong immunomodulatory effects. As such, these F-MSCs can be viewed as alternative sources of MSCs. We review here the current understanding of the mechanisms behind the immunomodulatory properties of BM MSCs and F-MSCs. An increase in our understanding of MSC suppressor mechanisms will offer insights for prevalent clinical use of these versatile adult stem cells in the near future.
Overexpression of Insig-1 protects β cell against glucolipotoxicity via SREBP-1c
Authors: Chen Ke , jin ping , He Hong-hui , Xie Yan-hong , Xie Xiao-yun , Mo Zhao-hui 
Published: August 2011

Abstract

Background
High glucose induced lipid synthesis leads to β cell glucolipotoxicity. Sterol regulatory element binding protein-1c (SREBP-1c) is reported to be partially involved in this process. Insulin induced gene-1 (Insig-1) is an important upstream regulator of Insig-1-SREBPs cleavage activating protein (SCAP)-SREBP-1c pathway. Insig-1 effectively blocks the transcription of SREBP-1c, preventing the activation of the genes for lipid biosynthesis. In this study, we aimed to investigate whether Insig-1 protects β cells against glucolipotoxicity.

Methods
An Insig-1 stable cell line was generated by overexpression of Insig-1 in INS-1 cells. The expression of Insig-1 was evaluated by RT-PCR and Western blotting, then, cells were then treated with standard (11.2 mM) or high (25.0 mM) glucose for 0 h, 24 h and 72 h. Cell viability, apoptosis, glucose stimulated insulin secretion (GSIS), lipid metabolism and mRNA expression of insulin secretion relevant genes such as IRS-2, PDX-1, GLUT-2, Insulin and UCP-2 were evaluated.

Results
We found that Insig-1 suppressed the high glucose induced SREBP-1c mRNA and protein expression. Our results also showed that Insig-1 overexpression protected β cells from ER stress-induced apoptosis by regulating the proteins expressed in the IRE1α pathway, such as p-IRE1α, p-JNK, CHOP and BCL-2. In addition, Insig-1 up-regulated the expression of IRS-2, PDX-1, GLUT-2 and Insulin, down-regulated the expression of UCP-2 and improved glucose stimulated insulin secretion (GSIS). Finally, we found that Insig-1 inhibited the lipid accumulation and free fatty acid (FFA) synthesis in a time-dependent manner.

Conclusions
There results suggest that Insig-1 may play a critical role in protecting β cells against glucolipotoxicity by regulating the expression of SREBP-1c.
Kinome expression profiling and prognosis of basal breast cancers
Authors: Sabatier Renaud , Finetti Pascal , Mamessier Emilie , Raynaud Stéphane , Cervera Nathalie , Lambaudie Eric , Jacquemier Jocelyne , Viens Patrice , Birnbaum Daniel , Bertucci François 
Published: August 2011

Abstract

Background
Basal breast cancers (BCs) represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- versus poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES). Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling.

Methods
DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS) in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set.

Results
A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73). This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518) sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS versus 54% for other patients (p = 1.62E-4, log-rank test).

Conclusions
Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.
Media composition influences yeast one- and two-hybrid results
Authors: Liu Ying , Merchant Zabeena , Hsiao Hao-Ching , Gonzalez Kim L , Matthews Kathleen S , Bondos Sarah E 
Published: August 2011

Abstract
Although yeast two-hybrid experiments are commonly used to identify protein interactions, the frequent occurrence of false negatives and false positives hampers data interpretation. Using both yeast one-hybrid and two-hybrid experiments, we have identified potential sources of these problems: the media preparation protocol and the source of the yeast nitrogen base may not only impact signal range but also effect whether a result appears positive or negative. While altering media preparation may optimize signal differences for individual experiments, media preparation must be reported in detail to replicate studies and accurately compare results from different experiments.
Fabrication of flexible UV nanoimprint mold with fluorinated polymer-coated PET film
Authors: Shin Ju-Hyeon , Lee Seong-Hwan , Byeon Kyeong-Jae , Han Kang-Soo , Lee Heon , Tsunozaki Kentaro 
Published: August 2011

Abstract
UV curing nanoimprint lithography is one of the most promising techniques for the fabrication of micro- to nano-sized patterns on various substrates with high throughput and a low production cost. The UV nanoimprint process requires a transparent template with micro- to nano-sized surface protrusions, having a low surface energy and good flexibility. Therefore, the development of low-cost, transparent, and flexible templates is essential. In this study, a flexible polyethylene terephthalate (PET) film coated with a fluorinated polymer material was used as an imprinting mold. Micro- and nano-sized surface protrusion patterns were formed on the fluorinated polymer layer by the hot embossing process from a Si master template. Then, the replicated pattern of the fluorinated polymer, coated on the flexible PET film, was used as a template for the UV nanoimprint process without any anti-stiction coating process. In this way, the micro- to nano-sized patterns of the original master Si template were replicated on various substrates, including a flat Si substrate and curved acryl substrate, with high fidelity using UV nanoimprint lithography.
What do we have to know from migrants' past exposures to understand their health status? a life course approach
Authors: Spallek Jacob , Zeeb Hajo , Razum Oliver 
Published: August 2011

AbstractEmpirical findings show that morbidity and mortality risks of migrants can differ considerably from those of populations in the host countries. However, while several explanatory models have been developed, most migrant studies still do not consider explicitly the situation of migrants before migration. Here, we discuss an extended approach to understand migrant health comprising a life course epidemiology perspective.The incorporation of a life course perspective into a conceptual framework of migrant health enables the consideration of risk factors and disease outcomes over the different life phases of migrants, which is necessary to understand the health situation of migrants and their offspring. Comparison populations need to be carefully selected depending on the study questions under consideration within the life course framework.Migrant health research will benefit from an approach using a life course perspective. A critique of the theoretical foundations of migrant health research is essential for further developing both the theoretical framework of migrant health and related empirical studies.
Birth outcomes in South African women receiving highly active antiretroviral therapy: a retrospective observational study
Authors: van der Merwe Karin , Hoffman Risa , Black Vivian , Chersich Matthew , Coovadia Ashraf , Rees Helen 
Published: August 2011

BackgroundUse of highly active antiretroviral therapy (HAART), a triple‐drug combination, in HIV‐infected pregnant women markedly reduces mother to child transmission of HIV and decreases maternal morbidity. However, there remains uncertainty about the effects of in utero exposure to HAART on foetal development.MethodsOur objectives were to investigate whether in utero exposure to HAART is associated with low birth weight and/or preterm birth in a population of South African women with advanced HIV disease. A retrospective observational study was performed on women with CD4 counts ≤250 cells/mm3 attending antenatal antiretroviral clinics in Johannesburg between October 2004 and March 2007. Low birth weight (<2.5 kg) and preterm birth rates (<37 weeks) were compared between those exposed and unexposed to HAART during pregnancy. Effects of different HAART regimen and duration were assessed.ResultsAmong HAART‐unexposed infants, 27% (60/224) were low birth weight compared with 23% (90/388) of early HAART‐exposed (exposed <28 weeks gestation) and 19% (76/407) of late HAART‐exposed (exposed ≥28 weeks) infants (p = 0.05). In the early HAART group, a higher CD4 cell count was protective against low birth weight (AOR 0.57 per 50 cells/mm3 increase, 95% CI 0.45‐0.71, p < 0.001) and preterm birth (AOR 0.68 per 50 cells/mm3 increase, 95% CI 0.55‐0.85, p = 0.001). HAART exposure was associated with an increased preterm birth rate (15%, or 138 of 946, versus 5%, or seven of 147, in unexposed infants, p = 0.001), with early nevirapine and efavirenz‐based regimens having the strongest associations with preterm birth (AOR 5.4, 95% CI 2.1‐13.7, p < 0.001, and AOR 5.6, 95% CI 2.1‐15.2, p = 0.001, respectively).ConclusionsIn this immunocompromised cohort, in utero HAART exposure was not associated with low birth weight. An association between NNRTI‐based HAART and preterm birth was detected, but residual confounding is plausible. More advanced immunosuppression was a risk factor for low birth weight and preterm birth, highlighting the importance of earlier HAART initiation in women to optimize maternal health and improve infant outcomes.
Anastomosing Hemangioma of the Genitourinary System
Authors: Kryvenko Oleksandr N. , Gupta Nilesh S. , Meier Frederick A. , Lee Min W. , Epstein Jonathan I. 
Published: August 2011

Abstract
We describe 3 ovarian and 5 renal anastomosing hemangiomas. One manifested with polycythemia, others were incidental; none recurred. The mean patient age was 58 years. Three hemangiomas developed in end-stage renal disease. Tumors were well-demarcated, mahogany brown, spongy lesions measuring 0.1 to 5 cm. Tortuous large vessels fed and drained tightly packed anastomosing sinusoidal capillary channels. Four hemangiomas exhibited lobular architecture, central edema/hyalinization, and intravascular growth. Five cases had thrombosis, hemorrhage, and hemosiderin. One ovarian tumor induced stromal luteinization. Three tumors had foci of extramedullary hematopoiesis (one associated with polycythemia). Six cases demonstrated eosinophilic intracytoplasmic globules. Three cases included hobnail endothelial cells. Atypia was minimal and mitoses were absent in all cases. We find this vascular neoplasm unique for the genitourinary system. Despite selected features mimicking angiosarcoma, our data support its benign nature. The current study expands the gross and radiographic appearance, clinical aspects, and ultrastructure, with the first report of the lesion occurring in the ovary.