tbuckley/cabot-search huggingface dataset:
Stereotactic Radiosurgery Plus Whole-Brain Radiation Therapy vs Stereotactic Radiosurgery Alone for Treatment of Brain Metastases
Authors: Hidefumi Aoyama, Hiroki Shirato, Masao Tago, Keiichi Nakagawa, Tatsuya Toyoda, Kazuo Hatano, Masahiro Kenjyo, Natsuo Oya, Saeko Hirota, Hiroki Shioura, Etsuo Kunieda, Taisuke Inomata, Kazushige Hayakawa, Norio Katoh, Gen Kobashi
Journal: JAMA (2006)

In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone.To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death.Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003.Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients).The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death.The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation.Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used.umin.ac.jp/ctr Identifier: C000000412.
Alternative expression of TCRζ related genes in patients with chronic myeloid leukemia
Authors: Xianfeng Zha, Xiaojuan Yan, Qi Shen, Yuping Zhang, Xiuli Wu, Shaohua Chen, Bo Li, Lijian Yang, Suxia Geng, Jianyu Weng, Xin Du, Yangqiu Li
Journal: Journal of Hematology & Oncology (2012)

Abstract A previous study has demonstrated a significant decrease in the TCRζ gene expression level in chronic myeloid leukemia (CML); thus, we further investigated the expression of TCRζ-regulating factors, the distribution of the TCRζ 3' untranslated region (3'-UTR) splice variants, and the expression level and correlation of the alternative splicing factor/splicing factor 2 (ASF/SF-2), FcεRIγ and ZAP-70 genes. TCRζ 3'-UTR splice variants were identified in peripheral blood mononuclear cells (PBMCs) from 14 healthy individuals, 40 patients with CML and 22 patients with CML in complete remission (CML-CR) by RT-PCR. The expression level of the TCRζ, FcεRIγ, ASF/SF-2 and ZAP-70 genes was analyzed by real-time quantitative PCR. While the expression of TCRζ gene in the CML group was significantly lower than that in the healthy individual and CML-CR groups, a significantly higher expression of the FceRIγ and ASF/SF-2 genes was found in the CML group. Two types of splicing forms were detected in all of the healthy individual CML-CR cases: wild type (WT) TCRζ 3'-UTR and alternatively splieced (AS) TCRζ 3'-UTR which have been alternatively splieced in the WT TCRζ 3'-UTR . However, 35% of the CML cases contained only the wild type TCRζ 3'-UTR isoform. Based on the TCRζ 3'-UTR isoform expression characteristic, we divided the patients with CML into two subgroups: the WT + AS - CML group, containing patients that express only the wild type TCRζ 3'-UTR, and the WT + AS + CML group, which contained patients that expressed two TCRζ 3'-UTR isoforms. A significantly different ASF/SF-2 and FcεRIγ gene expression pattern was found between the WT + AS - and WT + AS + CML groups. We concluded that defective TCRζ expression may be characterized in the WT + AS - and WT + AS + CML subgroups by the different gene expression pattern. The overexpression of ASF/SF2, which alternatively splices the TCRζ 3’-UTR, is thought to participate in feedback regulation. The characteristics of TCRζ 3'-UTR alternative splicing may be a novel immunological marker for the evaluation of the CML immune status.
Agreement Between Self-Reported Breast Cancer Treatment and Medical Records in a Population-Based Breast Cancer Family Registry
Authors: Kelly-Anne Phillips, Roger L. Milne, Saundra Buys, Michael L. Friedlander, John H. Ward, Margaret R.E. McCredie, Graham G. Giles, John L. Hopper
Journal: Journal of Clinical Oncology (2005)

Purpose Although self-report data on treatment for breast cancer are collected in some large epidemiologic studies, their accuracy is unknown. Methods As part of a population-based Breast Cancer Family Registry, questionnaires on initial breast cancer treatment and subsequent recurrence were mailed to Australian women diagnosed between 1991 and 1998. These self-report data were validated against medical records for 895 women. Results The median recall period was 3.2 years, mean age at diagnosis was 44 years, and 81% of women had early-stage breast cancer. Agreement between the two data sources was very high for general questions about type of treatment (100%, 99%, 99%, and 94% for surgery, radiotherapy, chemotherapy, hormonal therapy, respectively). For more specific questions about details of each treatment received, agreement was: for radiation therapy, 96% and 99% for radiation to the breast and chest wall, respectively; for surgery, 83%, 97%, and 88% for lumpectomy, mastectomy, and lymph node dissection, respectively; for hormonal therapy, 94% for tamoxifen; and for chemotherapy, range between 76% and 93%. There was 97% agreement about whether there had been a recurrence, and agreement about the location of recurrence was at least 90% for all sites. Agreement regarding stage at diagnosis was 62%, with discrepancies mostly due to women with locoregional disease incorrectly reporting distant spread. Conclusion This self-report questionnaire can be used to collect accurate data on broad categories of initial breast cancer treatment and recurrence, and even for more detailed information on specifics of treatment and site of recurrence.
Molecular Regulation of B Lymphocyte Response
Authors: T Kishimoto, T Hirano
Journal: Annual Review of Immunology (1988)

Antibodies are one of the key elements in the immune system. On the one hand, they play an essential role in protection against viral and bacterial infections; on the other hand, they are involved in certain autoimmune diseases and in immediate-type hypersensivity. B cells are the only euka­ ryotic cells that can produce antibody molecules. The regulated production of antibody molecules is one of the most complex examples of eukaryotic cell differentiation and one of those most. amenable to scientific in­ vestigation. Since the discovery of T and B cell interaction in the antibody response, the mechanism of the regulatory function(s) ofT cells in the B cell response has been one of the central issues in immunology. The existence ofT cell­ derived helper factors that promote B cell proliferation and antibody secretion was recognized in the early and mid 1970s. Dutton and his colleagues (1) as well as Schimpl & Wecker (2) demonstrated that culture supernatants of murine T cells stimulated by mixed lymphocyte reaction or by T cell mitogens could reconstitute the antibody response of T cell­ depleted splenic lymphocytes. Kishimoto and his colleagues (3) showed that anti-immunoglobulin (anti-Ig) and T cell--wnditioned medium could induce Ig secretion in rabbit B cells, indicating that two totally antigen­ nonspecific signals (i.e. cross-linking Ig-receptors and T cell-derived helper factors) could induce Ig production in B cells. Subsequently, the results obtained with rabbit B cells were confirmed in the murine system. Parker and his colleagues (4) could induce Ig secretion in murine B cells with in solubilized anti-Ig and culture supernatants of concanavalin A (Con A)­ stimulated T cells. All of these results indicated that the helper function of T cells in antibody response was mediated by soluble factors.
Spanish move away from Mediterranean diet
Authors: M. de Lago
Journal: BMJ (2011)

Spain, one of the countries where the Mediterranean diet prevails, is moving away from some of the nutritional habits that are associated with a lower risk of coronary disease.

In particular, Spanish people are eating more baked goods and less fruits, cereals, and vegetables—items typically plentiful in the Mediterranean diet.

The trend has emerged from data gathered by the first national food intake survey in 2010, published by the Spanish Food Security and Nutrition Agency last week; the annual survey carried out jointly by the Spanish Environment Ministry and the Foundation of Nutrition between 2000 and 2006; and three other surveys (in 1964, 1981, and 1991) …
Randomized Trial of 13-<i>cis</i> Retinoic Acid Compared With Retinyl Palmitate With or Without Beta-Carotene in Oral Premalignancy
Authors: Vassiliki A. Papadimitrakopoulou, J. Jack Lee, William N. William, Jack W. Martin, Margaret Thomas, Edward S. Kim, Fadlo R. Khuri, Dong M. Shin, Lei Feng, Waun Ki Hong, Scott M. Lippman
Journal: Journal of Clinical Oncology (2008)

Purpose To investigate whether retinyl palmitate (RP) alone or plus beta-carotene (BC) would be as effective and less toxic than low-dose 13-cis retinoic acid (13cRA) in treating oral premalignant lesions (OPLs) and reducing the risk of oral cancer. Patients and Methods Initially, patients were randomly assigned to receive low-dose 13cRA or BC plus RP for 3 years (plus 2 years follow-up). After other randomized trials established an adverse effect of BC on lung cancer incidence/mortality, BC was dropped (patients randomly assigned to 13cRA or RP alone). The primary end point was OPL clinical response at 3 months. Results We randomly assigned 162 eligible patients. The 3-month clinical response rate of the combined BC plus RP and RP alone arm (32.5%) was not statistically equivalent to that of 13cRA (48.1%). The clinical response rate of RP alone (20.0%) was significantly lower than that of BC plus RP (42.9%; P = .03). Similar oral cancer–free survival rates were observed across all arms. There was no significant association between 3-month OPL response and subsequent oral cancer development (P = .11). Grades 2 and higher adverse events were more common in the 13cRA than other groups (P &lt; .0001). Conclusion This large chemoprevention trial did not establish the equivalence of RP plus BC or RP alone with low-dose 13cRA in reducing the long-term risk of oral cancer. At present, 13cRA, BC plus RP, and RP alone cannot be recommended for chemoprevention, and new, better agents are needed in this setting. Our results did not establish short-term OPL response as a surrogate end point for oral cancer–free survival.
Glycopeptide storage in skin fibroblasts cultured from a patient with alpha-mannosidase deficiency.
Authors: G C Tsay, G Dawson, R Matalon
Journal: Journal of Clinical Investigation (1975)

Patients with mannosidosis, an inherited deficiency of lysosomal alpha-mannosidase, accumulate large amounts of mannose-rich oligosaccharides (the "core" of the carbohydrate units of many glocoproteins) in brain and liver and excrete these partial degradation products in their urine. A profound alpha-mannosidase deficiency was demonstrated in fibroblasts cultured from a skin biopsy obtained from a child with mannosidosis. Further, abnormal glycopeptides rich in mannose and similar to oligosaccharides found in the patient's urine were isolated from fibroblast extracts by a variety of chromatographic procedures and by virtue of their binding to a concanavalin A-Sepharose 4B affinity column. This storage material contained mannose, N-acetylglucosamine, and asparagine in the ratio 3 : 1 : 1 together with a few toher amino acids and had a molecular weight of approximately 1,100. There was no evidence for excretion of storage material by mannosidosis fibroblasts or for any abnormality in cell surface glycoprotein composition. The glycopeptide nature of the storage material isolated from cultured skin fibroblasts may be attributed to the low level of N-aspartyl-beta-glucosamindase (EC 3.5.1.-) activity in these cells.
Respiratory muscle force and ventilatory function in adolescents
Authors: PC Schrader, PH Quanjer, IC Olievier
Journal: European Respiratory Journal (1988)

In 94 girls and 90 boys, aged 12.5-20.3 yr, the relationship of respiratory pressures or forces with lung volumes and ventilatory flows was studied. There was great variability in respiratory muscle performance, which helps to explain differences in lung volumes between individuals. Respiratory muscle force increases almost proportionally with thoracic dimensions, so that inspiratory and expiratory pressures generated at the level of residual volume (RV), functional residual capacity (FRC) and total lung capacity (TLC) are approximately constant with age. In the oldest boys there is evidence that the continued increase in lung volumes when they stop growing is due to a 'muscularity effect'. Boys generate larger pressures than girls at all lung volumes. Thus boys attain a larger TLC, and in spite of narrower airways, the same peak expiratory flow and a larger FIV1/FVC ratio than girls. Effort independent flows (FEV1 and MMEF), however, are larger in girls.
IgG autoantibodies bound to surfaces of necrotic cells and complement C4 comprise the phagocytosis promoting activity for necrotic cells of systemic lupus erythaematosus sera
Authors: G E Grossmayer, L E Munoz, C K Weber, S Franz, R E Voll, P M Kern, J R Kalden, G Schett, M Herrmann, U S Gaipl
Journal: Annals of the Rheumatic Diseases (2007)

Accumulation of dying and dead cells is thought to be involved in the etiopathogenesis of systemic lupus erythaematosus (SLE). Clearance has been described mainly for apoptotic cells; however, the knowledge of serum factors participating in the phagocytosis of necrotic cells is limited.Sera from 18 patients with SLE and 10 normal healthy donors (NHD), and macrophages from 3 NHD were included. Autoantibodies and complement were measured by ELISA and phagocytosis by flow cytometry. Binding of serum IgG to necrotic cells was assessed by flow cytometry and confocal microscopy.Sera from patients with SLE and NHD generally promoted the phagocytosis of necrotic cells by macrophages isolated from NHD. Five independent experiments with macrophages from three different NHD led to similar results. The sera from healthy controls displayed a homogeneous activity, whereas sera from patients with SLE showed a dichotomic behaviour. Only sera containing autoantibodies binding to the surfaces of necrotic cells and sufficient complement showed increased phagocytosis promoting activities. In SLE sera, C4 turned out to be the critical complement component in this process. Sera de-complemented by heat treatment strongly reduced phagocytosis of necrotic cells.Serum components influence the uptake of necrotic cells by phagocytosis competent macrophages from NHD. Complement is required for this process and autoantibodies binding to the surfaces of necrotic cells additionally promote their phagocytosis.
Direct Conversion of Adult Skin Fibroblasts to Endothelial Cells by Defined Factors
Authors: Jung-Kyu Han, Sung-Hwan Chang, Hyun-Ju Cho, Saet-Byeol Choi, Hyo-Suk Ahn, Jaewon Lee, Heewon Jeong, Seock-Won Youn, Ho-Jae Lee, Yoo-Wook Kwon, Hyun-Jai Cho, Byung-Hee Oh, Peter Oettgen, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2014)

Background— Cell-based therapies to augment endothelial cells (ECs) hold great therapeutic promise. Here, we report a novel approach to generate functional ECs directly from adult fibroblasts. Methods and Results— Eleven candidate genes that are key regulators of endothelial development were selected. Green fluorescent protein (GFP)–negative skin fibroblasts were prepared from Tie2-GFP mice and infected with lentiviruses allowing simultaneous overexpression of all 11 factors. Tie2-GFP + cells (0.9%), representing Tie2 gene activation, were detected by flow cytometry. Serial stepwise screening revealed 5 key factors (Foxo1, Er71, Klf2, Tal1, and Lmo2) that were required for efficient reprogramming of skin fibroblasts into Tie2-GFP + cells (4%). This reprogramming strategy did not involve pluripotency induction because neither Oct4 nor Nanog was expressed after 5 key factor transduction. Tie2-GFP + cells were isolated using fluorescence-activated cell sorting and designated as induced ECs (iECs). iECs exhibited endothelium-like cobblestone morphology and expressed EC molecular markers. iECs possessed endothelial functions such as Bandeiraea simplicifolia -1 lectin binding, acetylated low-density lipoprotein uptake, capillary formation on Matrigel, and nitric oxide production. The epigenetic profile of iECs was similar to that of authentic ECs because the promoters of VE-cadherin and Tie2 genes were demethylated. mRNA profiling showed clustering of iECs with authentic ECs and highly enriched endothelial genes in iECs. In a murine model of hind-limb ischemia, iEC implantation increased capillary density and enhanced limb perfusion, demonstrating the in vivo viability and functionality of iECs. Conclusions— We demonstrated the first direct conversion of adult fibroblasts to functional ECs. These results suggest a novel therapeutic modality for cell therapy in ischemic vascular disease.
Long non-coding RNA<i>HNF1A-AS1</i>regulates proliferation and migration in oesophageal adenocarcinoma cells
Authors: Xue Yang, Jee Hoon Song, Yulan Cheng, Wenjing Wu, Tushar Bhagat, Yiting Yu, John M Abraham, Sariat Ibrahim, William Ravich, Bani Chander Roland, Mouen Khashab, Vikesh K Singh, Eun Ji Shin, Xiao Yang, Amit K Verma, Stephen J Meltzer, Yuriko Mori
Journal: Gut (2013)

<h3>Objectives</h3> Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of cancer. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of oesophageal adenocarcinoma (EAC) and its progression. <h3>Design</h3> lncRNAs that are abnormally upregulated in EACs were identified by RNA-sequencing analysis, followed by quantitative RT-PCR (qRTPCR) validation using tissues from 25 EAC patients. Cell biological assays in combination with small interfering RNA-mediated knockdown were performed in order to probe the functional relevance of these lncRNAs. <h3>Results</h3> We discovered that a lncRNA, <i>HNF1A-AS1</i>, is markedly upregulated in human primary EACs relative to their corresponding normal oesophageal tissues (mean fold change 10.6, p&lt;0.01). We further discovered that <i>HNF1A-AS1</i> knockdown significantly inhibited cell proliferation and anchorage-independent growth, suppressed S-phase entry, and inhibited cell migration and invasion in multiple in vitro EAC models (p&lt;0.05). A gene ontological analysis revealed that <i>HNF1A-AS1</i> knockdown preferentially affected genes that are linked to assembly of chromatin and the nucleosome, a mechanism essential to cell cycle progression. The well known cancer-related lncRNA, <i>H19</i>, was the gene most markedly inhibited by <i>HNF1A-AS1</i> knockdown. Consistent to this finding, there was a significant positive correlation between <i>HNF1A-AS1</i> and <i>H19</i> expression in primary EACs (p&lt;0.01). <h3>Conclusions</h3> We have discovered abnormal upregulation of a lncRNA, <i>HNF1A-AS1</i>, in human EAC. Our findings suggest that dysregulation of <i>HNF1A-AS1</i> participates in oesophageal tumorigenesis, and that this participation may be mediated, at least in part, by modulation of chromatin and nucleosome assembly as well as by <i>H19</i> induction.
Face mask spirometry and respiratory pressures in normal subjects
Authors: M. Wohlgemuth, E.L. van der Kooi, J.C. Hendriks, G.W. Padberg, H.T. Folgering
Journal: European Respiratory Journal (2003)

Spirometry and maximal respiratory pressures are pulmonary function parameters commonly used to evaluate respiratory function. Prediction values are available for conventional lung function devices using a standard tube or flanged type of mouthpiece connection. This equipment is not suitable for patients with facial or buccal muscle weakness, because of air leakage around the mouthpiece. A face mask was used for the portable lung function devices used in the neuromuscular department. The aim of this study was to compare the face mask and the conventional mouthpiece for the measurement of spirometry and of respiratory pressures in 22 healthy subjects. Values obtained with the conventional mouthpiece differed significantly from values obtained with the face mask. With the mask, forced vital capacity and forced expiratory volume in one second were 200 mL lower, and maximal expiratory pressure was 3.2 kPa lower than with the mouthpiece. Subsequently, new prediction values for face mask spirometry and maximal respiratory pressures were obtained from 252 other healthy subjects, from which new prediction equations were derived. It was concluded that the face mask connection to the lung function device is a valid alternative, is easy to use and is most useful to monitor changes in patients. This study confirms the importance of appropriate prediction equations, depending on subject-instrument interfaces.
Making the blastocyst: lessons from the mouse
Authors: Katie Cockburn, Janet Rossant
Journal: Journal of Clinical Investigation (2010)

Mammalian preimplantation development, which is the period extending from fertilization to implantation, results in the formation of a blastocyst with three distinct cell lineages. Only one of these lineages, the epiblast, contributes to the embryo itself, while the other two lineages, the trophectoderm and the primitive endoderm, become extra-embryonic tissues. Significant gains have been made in our understanding of the major events of mouse preimplantation development, and recent discoveries have shed new light on the establishment of the three blastocyst lineages. What is less clear, however, is how closely human preimplantation development mimics that in the mouse. A greater understanding of the similarities and differences between mouse and human preimplantation development has implications for improving assisted reproductive technologies and for deriving human embryonic stem cells.