tbuckley/cabot-search huggingface dataset:
Centromere Protein H Is a Novel Prognostic Marker for Nasopharyngeal Carcinoma Progression and Overall Patient Survival
Authors: Wen-Ting Liao, Li-Bing Song, Hui-Zhong Zhang, Xing Zhang, Ling Zhang, Wan-Li Liu, Yan Feng, Bao-Hong Guo, Hai-Qiang Mai, Su-Mei Cao, Man-Zhi Li, Hai-De Qin, Yi-Xin Zeng, Mu-Sheng Zeng
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The aim of the present study was to analyze the expression of Centromere protein H (CENP-H), one of the fundamental components of the human active kinetochore, in nasopharyngeal carcinoma (NPC) and to correlate it with clinicopathologic data, including patient survival. Experimental Design: Using reverse transcription-PCR and Western blot, we detected the expression of CENP-H in normal nasopharyngeal epithelial cells, immortalized nasopharyngeal epithelial cell lines, and NPC cell lines. Using immunohistochemistry, we analyzed CENP-H protein expression in 160 clinicopathologically characterized NPC cases. Statistical analyses were applied to test for prognostic and diagnostic associations. Results: Reverse transcription-PCR and Western blot showed that the expression level of CENP-H was higher in NPC cell lines and in immortalized nasopharyngeal epithelial cells than in the normal nasopharyngeal epithelial cell line at both transcriptional and translational levels. By immunohistochemical analysis, we found that 76 of 160 (47.5%) paraffin-embedded archival NPC biopsies showed high expression of CENP-H. Statistical analysis showed that there was a significant difference of CENP-H expression in patients categorized according to clinical stage (P = 0.024) and T classification (P = 0.027). Patients with higher CENP-H expression had shorter overall survival time, whereas patients with lower CENP-H expression had better survival. A prognostic value of CENP-H was also found of the subgroup of N0-N1 tumor classification. Multivariate analysis showed that CENP-H expression was an independent prognostic indicator for patient's survival. Conclusions: Our results suggest that CENP-H protein is a valuable marker of NPC progression. High CENP-H expression is associated with poor overall survival in NPC patients.
Murine hematopoietic cells with pre-B or pre-B/myeloid characteristics are generated by in vitro transformation with retroviruses containing fes, ras, abl, and src oncogenes.
Authors: K L Holmes, J H Pierce, W F Davidson, H C Morse
Journal: The Journal of Experimental Medicine (1986)

In vitro infection of bone marrow or fetal liver cells with retroviruses containing fes, abl, ras, or src oncogenes resulted in the transformation of early B lineage cells. All cell lines tested possessed rearrangements at the Ig heavy chain locus and some had rearrangements at the K chain locus. The majority of the lines corresponded phenotypically to Lyb-2+, Ly-5(B220)+, ThB- large pre-B cells, although some were classified as pro-B cells because of their Lyb-2+, Ly-17+, Ly-5(B220)- phenotype. We identified two cell lines that contained subpopulations of cells that coexpressed the B lineage antigens Lyb-2 and Ly-5(B220) and the myeloid lineage antigen Mac-1. Single-cell FMF cloning of these subpopulations showed that Mac-1+ cells were derived from Mac-1- cells and that these Mac-1+-cloned cells further differentiated into cells with phenotypic and functional characteristics of mature macrophages.
Evidence for limited B-lymphopoiesis in adult rabbits.
Authors: M A Crane, M Kingzette, K L Knight
Journal: The Journal of Experimental Medicine (1996)

Rabbits are born with a limited VDJ gene repertoire formed primarily by rearrangement of one VH gene, VH1. The VDJ genes are undiversified at birth but become diversified by approximately 2 mo of age. To investigate more closely the time during which this diversity occurs, we determined the nucleotide sequences of VDJ genes from peripheral blood leukocytes taken from young rabbits at various time points, and we examined the extent of the diversification of the VDJ genes. At 4 wk of age there were, on average, 3 nucleotide changes per VH region, with approximately 75% of the genes showing some diversification. The number of nucleotide changes per VH region increased to 12 by 6-8 wk of age, and all but 1 of the 35 sequences analyzed were diversified. Because only a limited number of genes can be examined by nucleotide sequence analysis, we used an RNase protection assay to examine a large number of genes and we determined the level of undiversified VH1 mRNA in lymphoid organs of both young and adult rabbits. In young rabbits, we found a high level of undiversified VDJ genes, but the level was greatly reduced by 2 mo of age. By adulthood, essentially all VDJ genes of cells from appendix, peripheral blood, and bone marrow were diversified. Because we had expected B lymphopoiesis to be ongoing in the bone marrow of adult rabbits, we were surprised not to find undiversified VDJ genes from the newly generated B cells. Therefore, we searched for evidence of ongoing B lymphopoiesis in bone marrow by isolating and examining circular DNA for the presence of VD and DJ recombination signal joints. We found highly reduced levels of recombination signal joints in bone marrow of adult rabbits relative to the levels found in bone marrow of newborn rabbits. These data indicate that limited VD and DJ gene rearrangements occur in bone marrow of adult rabbits, and we therefore suggest that B lymphopoiesis is limited in adults.
Efficacy of Sunitinib and Sorafenib in Metastatic Papillary and Chromophobe Renal Cell Carcinoma
Authors: Toni K. Choueiri, Anne Plantade, Paul Elson, Sylvie Negrier, Alain Ravaud, Stephane Oudard, Ming Zhou, Brian I. Rini, Ronald M. Bukowski, Bernard Escudier
Journal: Journal of Clinical Oncology (2007)

Sunitinib and sorafenib are novel tyrosine kinase inhibitors (TKIs) that have shown significant clinical activity in metastatic clear cell renal cell carcinoma (RCC). The activity of sunitinib and sorafenib in non-clear cell histologies has not been evaluated.Clinical features at study entry and treatment outcomes were evaluated in patients with metastatic papillary RCC (PRCC) and chromophobe RCC (ChRCC) who received either sunitinib or sorafenib as their initial TKI treatment in five US and French institutions. Response rate and survival were documented. Fisher's exact test was used for categoric variables, and the Kaplan-Meier method was used to estimate survival.Fifty-three patients were included. The number of patients with papillary and chromophobe histologies was 41 (77%) and 12 (23%), respectively. Response rate, progression-free survival (PFS) time, and overall survival time for the entire cohort were 10%, 8.6 months, and 19.6 months, respectively. Three (25%) of 12 ChRCC patients achieved a response (two patients treated with sorafenib and one treated with sunitinib), and PFS was 10.6 months. Two (4.8%) of 41 PRCC patients achieved a response (both patients were treated with sunitinib). PFS for the whole cohort was 7.6 months. Sunitinib-treated PRCC patients had a PFS of 11.9 months compared with 5.1 months for sorafenib-treated patients (P < .001).Patients with PRCC and ChRCC may have prolonged PFS from sunitinib and sorafenib, although clinical responses remain overall low in PRCC. Additional prospective trials with these agents in non-clear cell RCC will further clarify their use in the future.
Improved Efficacy of Dendritic Cell–Based Immunotherapy by Cutaneous Laser Illumination
Authors: Xinyuan Chen, Qiyan Zeng, Mei X. Wu
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The present study investigates a convenient laser-based approach to enhance dendritic cell (DC) migration and improve DC-based immunotherapy in murine models. Experimental Design: Influence of laser illumination on dermal tissue microenvironment and migration of DCs following intradermal injection were determined by whole-mount immunohistochemistry, transmission electron microscope, and flow cytometry. We also investigated in vivo expansion of CTLs by flow cytometry, CTL activity by in vitro CTL assay, and antitumor efficacy of DC immunization following cutaneous laser illumination in both preventive and therapeutic tumor models. Results: Laser illumination was found to significantly enlarge perforations in the perilymphatic basement membrane, disarray collagen fibers, and disrupt cell–matrix interactions in the dermis. The altered dermal tissue microenvironment permitted more efficient migration of intradermally injected DCs from the dermis to the draining lymph nodes (dLN). Laser illumination also slightly but significantly enhanced the expression of costimulatory molecule CD80 and MHC I on inoculated DCs. As a result, more vigorous expansion of tumor-specific IFN-γ+CD8+ T lymphocytes and enhanced CTL activity against 4T1 but not irrelevant tumor cells were obtained in the laser-treated group over the control group. Laser-augmented DC immunization also completely abrogated early growth of 4T1 tumor and B16F10 melanoma in preventive tumor models and significantly extended the survival of 4T1-resected mice in a therapeutic tumor model. Conclusion: These data suggest a simple, safe, laser-based approach to significantly enhance DC-based immunotherapy. Clin Cancer Res; 18(8); 2240–9. ©2012 AACR.
Genotypes of NK Cell KIR Receptors, Their Ligands, and Fcγ Receptors in the Response of Neuroblastoma Patients to Hu14.18-IL2 Immunotherapy
Authors: David C. Delgado, Jacquelyn A. Hank, Jill Kolesar, David Lorentzen, Jacek Gan, Songwon Seo, KyungMann Kim, Suzanne Shusterman, Stephen D. Gillies, Ralph A. Reisfeld, Richard Yang, Brian Gadbaw, Kenneth B. DeSantes, Wendy B. London, Robert C. Seeger, John M. Maris, Paul M. Sondel
Journal: Cancer Research (2010)

Response to immunocytokine (IC) therapy is dependent on natural killer cells in murine neuroblastoma (NBL) models. Furthermore, killer immunoglobulin-like receptor (KIR)/KIR-ligand mismatch is associated with improved outcome to autologous stem cell transplant for NBL. Additionally, clinical antitumor response to monoclonal antibodies has been associated with specific polymorphic-FcγR alleles. Relapsed/refractory NBL patients received the hu14.18-IL2 IC (humanized anti-GD2 monoclonal antibody linked to human IL2) in a Children's Oncology Group phase II trial. In this report, these patients were genotyped for KIR, HLA, and FcR alleles to determine whether KIR receptor-ligand mismatch or specific FcγR alleles were associated with antitumor response. DNA samples were available for 38 of 39 patients enrolled: 24 were found to have autologous KIR/KIR-ligand mismatch; 14 were matched. Of the 24 mismatched patients, 7 experienced either complete response or improvement of their disease after IC therapy. There was no response or comparable improvement of disease in patients who were matched. Thus KIR/KIR-ligand mismatch was associated with response/improvement to IC (P = 0.03). There was a trend toward patients with the FcγR2A 131-H/H genotype showing a higher response rate than other FcγR2A genotypes (P = 0.06). These analyses indicate that response or improvement of relapsed/refractory NBL patients after IC treatment is associated with autologous KIR/KIR-ligand mismatch, consistent with a role for natural killer cells in this clinical response.
Spatial Distribution of Phase Singularities in Ventricular Fibrillation
Authors: Miguel Valderrábano, Peng-Sheng Chen, Shien-Fong Lin
Journal: Circulation (2003)

Background— Multiple excitation wavelets are present during ventricular fibrillation (VF). The underlying wavelet organization of VF is unclear. Phase singularities (PSs)—locations of ambiguous activation state—underlie reentry and wavelet splitting and represent the sources of VF. Understanding the mechanisms of PS formation might be important in the development of effective therapies for sudden death. Methods and Results— We performed voltage, phase, and PS mapping in fibrillating ventricles, applying an automated PS detection algorithm to optically recorded fibrillation signals. PS clustering was noted along epicardial vessels, ridges of endocardial trabeculae, and papillary muscle insertions. Microscopically, these locations correlated with areas of apposition of fibers with different angulations and intramural vessels. A total of 83.2% of PSs were formed at and meandered about these anatomic structures, which acted as stabilizers: PSs colocalizing at anatomic substrates had longer life spans than nonanatomic PS (82.46±60.8 versus 40.5±31.9 ms, P &lt;0.01). The RV endocardium had a higher PS incidence than the epicardium (42.3±9.2 versus 23.5±11.6 PS/s, P &lt;0.01). Autocorrelation showed that irregular behavior was spatially restricted to anatomic heterogeneities compared with other areas, which had nearly periodic behaviors. Simple spatial PS distributions underlay complex and variable activation patterns attributable to variable PS behaviors, life spans, and inter-PS interactions. Conclusions— PSs occur in a nonrandom spatial distribution and colocalize with normal anatomic heterogeneities. Varying PS behaviors and life spans but stable PS spatial distributions cause ever-changing activation patterns that characterize VF.
The ANO3/MUC15 locus is associated with eczema in families ascertained through asthma
Authors: Marie-Hélène Dizier, Patricia Margaritte-Jeannin, Anne-Marie Madore, Jorge Esparza-Gordillo, Miriam Moffatt, Eve Corda, Florent Monier, Michel Guilloud-Bataille, Andre Franke, Stephan Weidinger, Isabella Annesi-Maesano, Jocelyne Just, Isabelle Pin, Francine Kauffmann, William Cookson, Young-Ae Lee, Catherine Laprise, Mark Lathrop, Emmanuelle Bouzigon, Florence Demenais
Journal: Journal of Allergy and Clinical Immunology (2012)
Lamin expression in normal human skin, actinic keratosis, squamous cell carcinoma and basal cell carcinoma
Authors: C.M.L.J. Tilli, F.C.S. Ramaekers, J.L.V. Broers, C.J. Hutchison, H.A.M. Neumann
Journal: British Journal of Dermatology (2003)

Aberrant expression patterns of nuclear lamins have been described in various types of cancer depending on the subtype of cancer, its aggressiveness, proliferative capacity and degree of differentiation. In general, the expression of A-type lamins (lamins A and C) has been correlated with a non-proliferating, differentiated state of cells and tissues.To establish and compare the expression patterns of lamins in normal human skin, actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC).Expression patterns of the individual lamin subtypes were studied immunohistochemically. The proliferation capacity of the tumour cells was detected using a specific antibody to Ki-67, and was related to the A-type lamin expression patterns.In normal skin, lamin A was expressed in the suprabasal cell compartment of the epidermis, whereas the basal cells were mostly unstained. BCCs and SCCs stained positive in most cells, while the epidermis overlying BCC and SCC and the epidermis in AK stained homogeneously and strongly in the basal cells in addition to the suprabasal cells. Lamin C was expressed in some basal cells of normal epidermis while the suprabasal cells stained strongly positive. Both BCCs and SCCs stained strongly positive for lamin C, with the difference that in BCC the staining was predominantly present in nucleolar structures with occasional staining of the nuclear envelope. The epidermis overlying SCC showed strong positivity in the lamina of virtually all cells. The expression of lamin C in the basal cells of AK resembled the expression pattern seen in the epidermis overlying BCC, i.e. a nucleolar staining next to nuclear envelope staining. Lamin B1 and B2 were found in virtually all cells in normal epidermis, AK, BCC, SCC and the epidermis overlying cancer. The percentage of Ki-67-expressing cells was highest in BCC (45%), and gradually decreased via epidermis overlying BCC, AK, SCC, and epidermis overlying SCC, to normal skin (11%). Simultaneous expression of A-type lamins and Ki-67 occurred in approximately 50% of the proliferating (Ki-67 positive) cells in BCC and SCC.Significant changes occur in the expression patterns of A-type lamins in both premalignant and malignant lesions of the skin. The profound overlap of lamin A and Ki-67 staining patterns indicates that the proliferating tumour cells may obtain a certain degree of differentiation. Finally, lamin A expression in the basal cell layer of the apparently normal epidermis overlying BCC may suggest its involvement in the primary process.
Atypical patterns in portable monitoring for sleep apnoea: features of nocturnal epilepsy?
Authors: Liborio Parrino, Giulia Milioli, Andrea Grassi, Fernando De Paolis, Silvia Riccardi, Elena Colizzi, Marcello Bosi, Mario Giovanni Terzano
Journal: European Respiratory Journal (2012)

Atypical cardiorespiratory patterns can be found during routine clinical use of portable monitoring for diagnosis of sleep-disordered breathing (SDB). Over 1,000 consecutive portable recordings were analysed to study the potential ictal nature of stereotyped cardiorespiratory and motor patterns. Snoring, airflow, thoracic effort, pulse rate, body position, oxygen saturation and activity of the anterior tibialis muscles were quantified. Recordings showing stereotyped polygraphic patterns recurring throughout the night, but without the features of sleep apnoea (apnoea/hypopnoea index &lt;5 events·h −1 ), were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography. A total of 15 recordings showing repeated polygraphic patterns characterised by a sequence of microphone activation, respiratory activity atypical for sleep and wakefulness, heart rate acceleration and limb movements, followed by body position change, were selected for investigation. Once included in the study, patients underwent attended nocturnal video polysomnography that showed frontal epileptic discharges triggering periodic electroencephalographic arousals, autonomic activation and stereotyped motor patterns. A diagnosis of nocturnal frontal lobe epilepsy (NFLE) was established for all patients. NFLE should be taken into consideration in patients with stereotyped and recurrent behavioural features during portable monitoring carried out for diagnosis of SDB.
Investigation of the stability of apple allergen extracts
Authors: O. Rudeschko, B. Fahlbusch, M. Henzgen, G. Schlenvoigt, D. Herrmann, S. Vieths, L. Jäger
Journal: Allergy (1995)

To determine optimal conditions for allergen preservation, we investigated the influence of different stabilizing additives and of storage temperature on the allergen activity of apple protein preparations, obtained by extraction in phosphate buffer or by precipitation in diacetone alcohol and resolubilization in phosphate buffer in the presence or absence of enzyme inhibitors. For this purpose, the extracts were stored for 6 months either in frozen state at −20° C or in lyophilized state at −20° C, 4° C, or room temperature and were characterized by SDS‐PAGE, immunoblot, ELISA inhibition, and prick test. The highest stability revealed the extracts that were prepared by precipitation in the organic solvent in the presence of enzyme inhibitors, lyophilized, and stored at −20° C. For storage of extract solutions at 4° C, PBS/glycerol and cysteine/sodium citrate/glycerol were found to be the most effective stabilizing additives.
Language acquisition in the absence of experience
Authors: Stephen Crain
Journal: Behavioral and Brain Sciences (1991)

Abstract A fundamental goal of linguistic theory is to explain how natural languages are acquired. This paper describes some recent findings on how learners acquire syntactic knowledge for which there is little, if any, decisive evidence from the environment. The first section presents several general observations about language acquisition that linguistic theory has tried to explain and discusses the thesis that certain linguistic properties are innate because they appear universally and in the absence of corresponding experience. A third diagnostic for innateness, early emergence, is the focus of the second section of the paper, in which linguistic theory is tested against recent experimental evidence on children's acquisition of syntax.
THE INCIDENCE OF NOCTURNAL ENURESIS AFTER AGE FIVE
Authors: FREDERICK C. THORNE
Journal: American Journal of Psychiatry (1944)

Nocturnal enuresis persists into adult life much more commonly than generally recognized. Although normal children are supposed to gain bladder control before age 3, 16. 1 per cent of a group of 1000 consecutive selectees questioned at an army induction station reported enuresis after age 5. Two and one half per cent did not gain control until age 18 or later and isolated cases continued bed-wetting to age 33. Associated nervous or mental conditions were noted in 63 per cent of the cases reporting enuresis. A study of 369 inmates of a state school for mental defectives revealed enuresis in 83.8 per cent of a group of 54 idiots, 12.8 per cent of 164 imbeciles and only 4 per cent in 125 morons. It is suggested that nocturnal enuresis may frequently be regarded as a developmental defect which disappears spontaneously when maturation within the central nervous system is completed. Since the incidence of enuresis tends to decline with increasing creasing age it follows that almost any method of treatment will be effective if instituted at the proper time.
Effect of topical anti-inflammatory drugs on epithelial cell-induced eosinophil survival and GM-CSF secretion
Authors: J Roca-Ferrer, J Mullol, E Lopez, A Xaubet, L Pujols, JC Fernandez, C Picado
Journal: European Respiratory Journal (1997)

Topical anti-inflammatory drugs decrease eosinophil infiltration. This action may be due to an effect on the release of epithelial cell products responsible for promoting eosinophil survival. We investigated the effect of fluticasone propionate, budesonide, beclomethasone dipropionate and nedocromil sodium on the release of granulocyte/macrophage colony-stimulating factor (GM-CSF) and on eosinophil survival induced by secretions from cultured nasal epithelial cells. Human epithelial cell-conditioned media (HECM) were generated by cultured epithelial cells obtained from healthy subjects undergoing corrective nasal surgery. Normodense eosinophils isolated from peripheral blood were incubated with HECM generated with and without the drugs. All of the drugs tested inhibited eosinophil survival, and response was dose-dependent. Fluticasone propionate had the highest inhibitory potency (25% inhibitory concentration (IC25) 1x10(-9) M), followed by budesonide (IC25 3.3x10(-8) M), beclomethasone dipropionate (IC25 1.5x10(-6) M), and nedocromil sodium IC25 5x10(-6) M). Likewise, fluticasone was the strongest steroid in inhibiting release of GM-CSF (IC25 8.4x10(-11) M), followed by budesonide (IC25 2x10(-9) M), beclomethasone dipropionate (IC25 13x10(-8) M), and nedocromil sodium (IC25 &gt;10(-5) M). A significant correlation was found between both inhibitory effects (r=0.955; p&lt;0.05). Topical anti-inflammatory drugs may decrease eosinophil survival by abrogating the promoting effect of epithelial cells. These drugs may exert part of their therapeutic effect by modulating GM-CSF release. The following rank of potency was observed: fluticasone propionate &gt; budesonide &gt; beclomethasone dipropionate &gt; nedocromil sodium. The study of the interaction between epithelial cells and eosinophils may be a useful method for investigating and comparing the potency of topical drugs.