tbuckley/cabot-search huggingface dataset:
NF-kappa B mediated Up-regulation of CCCTC-binding factor in pediatric acute lymphoblastic leukemia
Authors: Han Zhang, Lin Zhu, Huacheng He, Shanshan Zhu, Wei Zhang, Xiao Liu, Xiaoxi Zhao, Chao Gao, Mei Mei, Shilai Bao, Huyong Zheng
Journal: Molecular Cancer (2014)

Acute lymphoblastic leukemia (ALL) is the most frequently occurring malignant neoplasm in children. Despite advances in treatment and outcomes for ALL patients, the pathogenesis of the disease remains unclear. Microarray analysis of samples from 100 Chinese children with ALL revealed the up-regulation of CTCF (CCCTC binding factor). CTCF is a highly conserved 11-zinc finger protein that is involved in many human cancers; however, the biological function of CTCF in pediatric ALL is unknown. The expression patterns of CTCF were evaluated in matched newly diagnosed (ND), complete remission (CR), and relapsed (RE) bone marrow samples from 28 patients. The potential oncogenic mechanism of CTCF and related pathways in leukemogenesis were investigated in leukemia cell lines. We identified significant up-regulation of CTCF in the ND samples. Importantly, the expression of CTCF returned to normal levels after CR but rebounded in the RE samples. In the pre-B ALL cell line Nalm-6, siRNA-mediated silencing of CTCF expression promoted cell apoptosis and reduced cell proliferation; accordingly, over-expression of a cDNA encoding full-length CTCF protected cells from apoptosis and enhanced cell proliferation. Furthermore, inhibition or activation of the nuclear factor-kappa B (NF-κB) pathway resulted in marked variations in the levels of CTCF mRNA and protein in leukemic cells, indicating that CTCF may be involved downstream of the NF-κB pathway. Moreover, inhibition of the NF-κB pathway increased cell apoptosis, which was partially rescued by ectopic over-expression of CTCF, suggesting that CTCF may play a significant role in the anti-apoptotic pathway mediated by NF-κB. Our results indicate that CTCF serves as both an anti-apoptotic factor and a proliferative factor in leukemic cells. It potentially contributes to leukemogenesis through the NF-κB pathway in pediatric ALL patients.
Long-term support of hematopoiesis by a single stem cell clone in patients with paroxysmal nocturnal hemoglobinuria
Authors: Jun-ichi Nishimura, Toshiyuki Hirota, Yuzuru Kanakura, Takashi Machii, Takashi Kageyama, Shoichi Doi, Hiroshi Wada, Toru Masaoka, Yoshio Kanayama, Hiroshi Fujii, Nobumasa Inoue, Maki Kuwayama, Norimitsu Inoue, Kazuhito Ohishi, Taroh Kinoshita
Journal: Blood (2002)
Silicosis in surface coalmine drillers.
Authors: D E Banks, M A Bauer, R M Castellan, N L Lapp
Journal: Thorax (1983)

Surface coalminers are generally thought to be at minimal risk of developing pneumoconiosis. Biopsy-proved silicoproteinosis was found in a 34-year-old surface coalmine driller, and two of nine other drill crew members who worked for the same company had chest radiographic findings compatible with simple silicosis. Reanalysis of data from a previous United States Public Health Service survey of surface coalminers, after exclusion of those with underground mining experience, showed that 38% of the cases of pneumoconiosis occurred in drill crew members, a group comprising only 11% of the study population. On the basis of these data surface coalmine drillers appear to have an increased risk of developing occupational lung disease.
Surface densities of diaphragmed fenestrae and transendothelial channels in different murine capillary beds.
Authors: A J Milici, N L'Hernault, G E Palade
Journal: Circulation Research (1985)

Fenestrated capillaries are provided with two types of regular discontinuities: fenestrae with negatively charged diaphragms, and transendothelial channels fitted with two diaphragms, of which the luminal one is uncharged. These structures are expected to affect macromolecular exchanges on the basis of size and charge. We have detected variations in the surface density of fenestrations and transendothelial channels (normalized to 1 micron of capillary endothelial profiles in sections) in selected areas of different murine organs, i.e., kidney cortex, duodenal mucosa, and exocrine pancreas. The survey was limited to endothelial segments less than or equal to 400 nm thick, and covered a total length of endothelial profiles of 1180 microns, 730 microns, and 1189 microns in the exocrine pancreas, intestinal mucosa, and kidney cortex, respectively. At least 1000 transendothelial openings were recorded by scoring for easily recognizable fenestrations, transendothelial channels, and unknowns, the latter representing either of the above in grazing sections. The linear density of all transendothelial openings taken together was found to vary among the different capillary beds (kidney cortex greater than intestinal mucosa greater than exocrine pancreas). This same sequence was observed for the linear densities of fenestrations, transendothelial channels, and unknowns considered individually. The values obtained were as follows: kidney cortex, 1.35 fenestrations per micron, 0.25 transendothelial channels per micron, 0.52 unknowns per micron; intestinal mucosa, 0.92 fenestrations per micron, 0.10 transendothelial channels per micron, 0.38 unknowns per micron; exocrine pancreas, 0.58 fenestrations per micron, 0.04 transendothelial channels per micron, 0.27 unknowns per micron. The differences in distribution of transendothelial openings among fenestrated capillary beds probably reflect capillary permeability modulations connected with the functions of these various organs.
Lower Switch Rate in Depressed Patients With Bipolar II Than Bipolar I Disorder Treated Adjunctively With Second-Generation Antidepressants
Authors: Lori L. Altshuler, Trisha Suppes, David O. Black, Willem A. Nolen, Gabriele Leverich, Paul E. Keck, Mark A. Frye, Ralph Kupka, Susan L. McElroy, Heinz Grunze, Christina M.R. Kitchen, Robert Post
Journal: American Journal of Psychiatry (2006)

OBJECTIVES: The authors compared the switch rate into hypomania/mania in depressed patients treated with second-generation antidepressants who had either bipolar I or bipolar II disorder. METHOD: In a 10-week trial, 184 outpatients with bipolar depression (134 with bipolar I disorder, 48 with bipolar II disorder, two with bipolar disorder not otherwise specified) were treated with one of three antidepressants as an adjunct to mood stabilizers. The patients’ switch rates were assessed. Switch was defined as a Young Mania Rating Scale (YMRS) score >13 or a Clinical Global Impression (CGI) mania score ≥3 (mildly ill). RESULTS: Depressed subjects with bipolar II disorder had a significantly lower acute switch rate into hypomania/mania when either YMRS or CGI criteria were used to define switch. CONCLUSIONS: These data suggest that depressed patients with bipolar II disorder are less vulnerable than those with bipolar I disorder to switch into hypomania/mania when treated with an antidepressant adjunctive to a mood stabilizer.
Cow's milk allergy: diagnostic accuracy of skin prick and patch tests and specific IgE
Authors: H Majamaa, P Moisio, H Kautiainen, H Majamaa, K Turjanmaa, K Holm
Journal: Allergy (1999)

Background: The objective of the present study was to evaluate the relevance of skin tests and the concentration of cow's milk‐specific IgE antibodies in correlation with oral cow's milk challenge in infants with suspected cow's milk allergy. Methods: The study material comprised 143 infants under the age of 2 years who had undergone a diagnostic elimination challenge because of suspected cow's milk allergy in 1996. Cow's milk‐specific IgE was measured, and skin prick and patch tests were performed. Results: Of the 143 oral cow's milk challenges performed, 72 (50%) were positive. Of the positive reactions, 22 involved immediate‐type reactions. In 50 patients, delayed‐onset reactions of eczematous or gastrointestinal type appeared. Of the infants with challenge‐proven cow's milk allergy, 26% showed elevated IgE concentrations to cow's milk, 14% had a positive skin prick test, and 44% had a positive patch test for cow's milk. Interestingly, in most patch test‐positive patients, the prick test for cow's milk was negative. Conclusions: Our study demonstrated that many patients with a negative prick test result had a positive patch test to cow's milk. The patch test was a more sensitive method than the prick test or RAST to detect cow's milk allergy in this study population. Our results indicate that patch testing will significantly increase the probability of early detection of cow's milk allergy. Confirmation of the diagnosis is essential in patients with negative test results but a clinical suspicion of food allergy, and in patch test‐positive patients. For this purpose, the most reliable method is the elimination‐challenge procedure.
Hierarchical self-tolerance to T cell determinants within the ubiquitous nuclear self-antigen La (SS-B) permits induction of systemic autoimmunity in normal mice.
Authors: P Reynolds, T P Gordon, A W Purcell, D C Jackson, J McCluskey
Journal: The Journal of Experimental Medicine (1996)

Systemic autoimmune diseases are frequently associated with clustering of high titer autoantibody responses towards nuclear self-antigens. Little is known, however, about the extent of immune tolerance to the target nuclear antigens or the events leading to the complex autoantibody responses that are characteristic of systemic autoimmunity. To address these issues, we have examined the mouse immune response to La autoantigen (mLa) and the homologous human La antigen (hLa), which are components of the La(SS-B)/Ro(SS-A) ribonucleoprotein (RNP) complex targeted in systemic lupus erythematosus and primary Sjögren's syndrome. The findings reveal the presence of hierarchical T cell tolerance involving multiple autodeterminants within the La autoantigen expressed by normal H-2k and H-2a mice. At one end of this spectrum, there was no detectable T or B cell autoimmunity observed in mice that were immunized with the immunodominant mLa287-301 determinant, which differed by a single residue in its core sequence from the homologous but highly immunogenic human La288-302 determinant. Interestingly, the mLa287-301 peptide acted as an altered peptide ligand that specifically antagonized the activation of an hLa288-302-specific T cell hybridoma. In contrast to the tolerogenic mLa287-301 determinant, a range of autoimmune potential was identified among poorly tolerizing, subdominant self-peptides present within mouse La autoantigen. Notably, immunization of normal mice with the autologous subdominant La25-44 and La106-129 determinants resulted in limited or no detectable autoantibody response. In contrast, immunization with the subdominant mouse La13-30 determinant induced a proliferative T cell response associated with the appearance of specific autoantibodies recognizing multiple intrastructural (La) and intermolecular components (Ro) of the murine La/Ro RNP. The findings suggest how diversified autoimmunity might follow initiation of immunity to simple peptide mimics of poorly tolerogenic determinants that are present within ubiquitous self-antigens.
The importance of defining left ventricular area at risk in vivo during acute myocardial infarction: an experimental evaluation with myocardial contrast two-dimensional echocardiography.
Authors: S Kaul, W Glasheen, T D Ruddy, N G Pandian, A E Weyman, R D Okada
Journal: Circulation (1987)

Because the left ventricular "area at risk" is the most important determinant of ultimate infarct size, it would be useful to know the size of the area at risk during acute myocardial infarction to make therapeutic decisions. We therefore performed a series of experiments in four groups of dogs. In group I dogs (n = 15) we attempted to determine whether current methods of assessing left ventricular function during acute myocardial infarction reflect the true size of the area at risk. At each of two to five sequential stages, a more proximal coronary occlusion was performed to produce a larger area at risk until cardiovascular collapse occurred. At each stage, the area at risk (measured by myocardial contrast echocardiography), hemodynamic variables, and left ventricular ejection fraction (LVEF) were measured. Hemodynamic variables became abnormal when the area at risk was large (25% to 40% of the left ventricle), whereas LVEF became abnormal when the area at risk was of moderate size (18%). When cardiac output and LVEF were normalized to baseline values, a close inverse relationship was noted between these variables and area at risk. In contrast, there was a poor relationship between normalized mean arterial pressure and area at risk (r = .42). In group II dogs (n = 9) the area at risk was measured serially over 6 hr after coronary occlusion. The size of the area at risk remained unchanged regardless of the transmural extent of the ultimate infarct. The circumferential endocardial extent of the area at risk closely predicted the circumferential endocardial extent of the infarct at 6 hr in eight of nine dogs that developed an infarct. Group III dogs (n = 7) underwent the same protocol as group II dogs, but the duration of occlusion was 3 hr. The circumferential endocardial extent of the area at risk closely predicted the circumferential endocardial extent of the infarct. Group IV dogs (n = 5) underwent subtotal coronary occlusion. Although regional wall motion abnormalities were noted in this group, no area at risk could be defined. We conclude that although a close inverse relationship is noted between normalized cardiac output and area at risk, the absolute values for cardiac output and other hemodynamic variables become abnormal only when the area at risk is large (25% to 40%); measurement of LVEF may provide a better assessment of the size of the area at risk than hemodynamic variables.(ABSTRACT TRUNCATED AT 400 WORDS)
Maximum volumes in excised human lungs: effects of age, emphysema, and formalin inflation.
Authors: N Berend, C Skoog, L Waszkiewicz, W M Thurlbeck
Journal: Thorax (1980)

The volume of air at a transpulmonary pressure (PL) of 25 cmH2O was measured in 28 emphysema-free and 39 emphysematous excised adult lungs and in the lungs of 53 infants and children. In the adult emphysema-free lungs, this volume (V25) was significantly correlated with body length in males but, corrected for body length, not significantly correlated with age in either males or females. V25 was on the average 20 per cent larger than predicted TLC in non-emphysematous lungs in vivo. The lungs were also inflated and fixed with formalin at a constant PL of 25 cm H2O and their volume measured (VL). Marked and variable underinflation compared to V25 occurred in the adult lungs and VL minus lung weight averaged 75% of V25 and 91% of predicted TLC. In infants and children, the ratio of VL minus lung weight to V25 averaged 1.08 with a range of 0.58 to 1.84. The larger the lungs, the smaller the ratio, suggesting that fixation played a role in producing the small VL. In the emphysematous lungs, a significant correlation between the degree of emphysema and V25 was found. However, a statistically significant increase in V25 only occurred when the emphysema grade was greater than 5.
Exploiting the superior protein resistance of polymer brushes to control single cell adhesion and polarisation at the micron scale
Authors: Julien E. Gautrot, Britta Trappmann, Fabian Oceguera-Yanez, John Connelly, Ximin He, Fiona M. Watt, Wilhelm T.S. Huck
Journal: Biomaterials (2010)

The control of the cell microenvironment on model patterned substrates allows the systematic study of cell biology in well defined conditions, potentially using automated systems. The extreme protein resistance of poly(oligo(ethylene glycol methacrylate)) (POEGMA) brushes is exploited to achieve high fidelity patterning of single cells. These coatings can be patterned by soft lithography on large areas (a microscope slide) and scale (substrates were typically prepared in batches of 200). The present protocol relies on the adsorption of extra-cellular matrix (ECM) proteins on unprotected areas using simple incubation and washing steps. The stability of POEGMA brushes, as examined via ellipsometry and SPR, is found to be excellent, both during storage and cell culture. The impact of substrate treatment, brush thickness and incubation protocol on ECM deposition, both for ultra-thin gold and glass substrates, is investigated via fluorescence microscopy and AFM. Optimised conditions result in high quality ECM patterns at the micron scale, even on glass substrates, that are suitable for controlling cell spreading and polarisation. These patterns are compatible with state-of-the-art technologies (fluorescence microscopy, FRET) used for live cell imaging. This technology, combined with single cell analysis methods, provides a platform for exploring the mechanisms that regulate cell behaviour.
Extended pelvic lymph node dissection in prostate cancer: a 20-year audit in a single center
Authors: F. Abdollah, N. Suardi, A. Gallina, M. Bianchi, M. Tutolo, N. Passoni, N. Fossati, M. Sun, P. dell'Oglio, A. Salonia, P.I. Karakiewicz, P. Rigatti, F. Montorsi, A. Briganti
Journal: Annals of Oncology (2013)
Blood lactate levels of decathletes during competition.
Authors: P Beaulieu, H Ottoz, C Grange, J Thomas, C Bensch
Journal: British Journal of Sports Medicine (1995)

There are many detailed physiological profiles of athletes who participate in a wide variety of sporting activities but few data have been obtained on decathletes. This study defines some physiological characteristics of these athletes and measures capillary lactate concentrations [La(b)] during a laboratory test of progressive maximal exhaustion and the different events during competition. The treadmill test is similar to the 100 m, 400 m and 1500 m in terms of [La(b)] accumulation but only similar to the 1500 m in terms of velocity. The 400 m is the most demanding event with the greatest blood lactate accumulation (mean(s.d.) 16.38(2.36) mmol l-1). The [La(b)] at the end of the 110 m hurdles is significantly lower than in any other racing events (mean(s.d.) 6.96(1.32) mmol l-1) compared with mean(s.d.) 12.14(2.87) and mean(s.d.) 11.44(2.16) for the 100 m and 1500 m respectively. The [La(b)] after the long jump, the high jump and the pole vault are not significantly different (mean(s.d.) 5.30(2.23), 4.64(1.39) and 5.36(1.34) mmol l-1) respectively).
‘To CT or not to CT? That is the question’: outcome surrogates for surveillance in childhood cystic fibrosis
Authors: Carolyn Young, Catherine Owens
Journal: Thorax (2012)

The benefit of the increasing utility of CT has been promoted as a potential long-term outcome surrogate for monitoring patients with cystic fibrosis (CF), and is recognised as a crucial part of CF research.1 The study by the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) on the use of thin-section CT highlights the sensitivity of this imaging modality in providing insight into the early development of CF lung disease. The factors associated with the development and progression of structural lung disease in infants and preschool children diagnosed by the newborn CF screening programme2 are described.

The argument for the increasing use of annual CT of the thorax as an outcome surrogate for measuring and monitoring the progression of lung disease in patients with CF is the ability of CT to detect subtle, salient lung parenchymal changes, as opposed to using conventional plain chest radiography or spirometry. However, lung clearance index (LCI), being more effective than spirometry, has been found to be as sensitive as high-resolution CT (HRCT) in detecting early lung abnormalities in infants, and together they compliment each other in providing markers for early CF lung disease in children.3 Application of LCI is suitable in all age groups, which suggests its potential as an outcome measure to monitor progression of disease throughout the life of patients with CF, and thus help reduce the cumulative radiation dose.4 5 It is suggested that, in clinical practice, LCI should be the first line of investigation to assess the presence of CF lung disease, and that HRCT should only be performed when LCI is normal. This is because a normal result on either measure is not predictive of a normal result in the other.3 This approach would reduce unnecessary CT imaging and the ensuing associated …
Don’t Deny Liver Transplantation to HIV Patients With Hepatocellular Carcinoma in the Highly Active Antiretroviral Therapy Era
Authors: Fabrizio Di Benedetto, Nicola De Ruvo, Massimiliano Berretta, Michele Masetti, Roberto Montalti, Stefano Di Sandro, Cristiano Quintini, Mauro Codeluppi, Umberto Tirelli, Giorgio E. Gerunda
Journal: Journal of Clinical Oncology (2006)
Molecular Evidence for Precambrian Origin of Amelogenin, the Major Protein of Vertebrate Enamel
Authors: Sidney Delgado, Didier Casane, Laure Bonnaud, Michel Laurin, Jean-Yves Sire, Marc Girondot
Journal: Molecular Biology and Evolution (2001)

Although molecular dating of cladogenetic events is possible, no molecular method has been described to date the acquisition of various tissues. Taking into account the specificity of the major protein in enamel in formation (amelogenin), we were able to develop such a method for enamel. Indeed, because the amelogenin protein is exclusively involved in enamel formation and mineralization and because it lacks pleiotropic effects, this protein is a good candidate to estimate the date of acquisition of this highly mineralized tissue. We searched DNA banks for similarities between the amelogenin sequence and other sequences. Similarities were found only to exon 2 of SPARC (osteonectin) in two protostomians and in eight deuterostomians, and to exon 2 of three SPARC-related deuterostomian genes (SC1, hevin, and QR1). The other amelogenin exons did not reveal significant similarities to other sequences. In these proteins, exon 2 mainly encodes the peptide signal that plays the essential role in enabling the protein to be ultimately localized in the extracellular matrix. We tested the significance of the exon 2 similarities. The observed values were always significantly higher than the expected randomly generated similarities. This demonstrates a common evolutionary origin of this exon. The phylogenetic analyses of exon 2 sequences indicated that exon 2 was duplicated to amelogenin from an ancestral SPARC sequence in the deuterostomian lineage before the duplication of deuterostomian SPARC and SC1/hevin/QR1. We were able to date the origin of the latter duplication at approximately 630 MYA. Therefore, amelogenin exon 2 was acquired before this date, in the Proterozoic, long before the so-called "Cambrian explosion," the sudden appearance of several bilateralian phyla in the fossil record at the Proterozoic-Phanerozoic transition. This sudden appearance has been often suggested to reflect intensive cladogenesis during this period. However, molecular dating of protostomian-deuterostomian divergence and of the cladogenesis among several major clades of Bilateralia lead to a different conclusion: many bilateralian clades were already present during the late Proterozoic. It has previously been proposed that these bilateralians were not mineralized and that they had low fossilization potential. Our results strongly suggest that late Proterozoic fossils possessing a mineralized tissue homologous to enamel might be found in the future.