tbuckley/cabot-search huggingface dataset:
Accumulation of Promoter Methylation Suggests Epigenetic Progression in Squamous Cell Carcinoma of the Esophagus
Authors: Mingzhou Guo, Jingli Ren, Michael G. House, Yu Qi, Malcolm V. Brock, James G. Herman
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Squamous esophageal cancer is common in non-Western countries and has a well-defined progression of preinvasive dysplasia leading to invasive squamous cell carcinoma. We examined the changes in promoter region methylation occurring during neoplastic progression. Experimental Design: The frequency of epigenetic changes in the promoter region of 14 genes epigenetically silenced in other cancers was determined and examined the most frequent changes in dysplastic lesions using methylation-specific PCR. Invasive squamous carcinomas, low to high grade dysplasia, and normal esophagus were then examined for methylation changes in the promoter region of each of the eight most commonly methylated genes. Results: Methylation was most frequent for CDKN2A/p16INK4a (52%) but was also common for O6-methylguanine-DNA methyltransferase, E-cadherin (CDH1), and retinoic acid receptor β2. Methylation at individual genes increased in frequency from normal to invasive cancer. Methylation of MLH1 was associated with microsatellite instability in most cases. The number of genes methylated in individual lesions increased as cellular atypia increased. In individual patients, cancers adjacent to dysplasia had the same epigenetic alterations as the less advanced lesions but often had additional methylation of other genes. Conclusions: These findings suggest that epigenetic progression parallels the histologic changes observed in the progression of squamous carcinoma of the esophagus.
The Src Family Tyrosine Kinase Fyn Regulates Natural Killer T Cell Development
Authors: Paul Gadue, Neil Morton, Paul L. Stein
Journal: The Journal of Experimental Medicine (1999)

T lymphocytes express two Src tyrosine kinases, Lck and Fyn. While thymocyte and T cell subsets are largely normal in fyn−/− mice, animals lacking Lck have impaired T cell development. Here, it is shown that Fyn is required for the rapid burst of interleukin (IL)-4 and IL-13 synthesis, which occurs promptly after T cell receptor activation. The lack of cytokine induction in fyn mutant mice is due to a block in natural killer (NK) T cell development. Studies using bone marrow chimeras indicate that the defect behaves in a cell-autonomous manner, and the lack of NK T cells is probably not caused by inappropriate microenvironmental cues. Both NK T cells and conventional T cells express similar levels of Lck, implying that Fyn and Lck have distinct roles in regulating NK T cell ontogeny. The fyn mutation defines the first signaling molecule that is selectively required for NK T cell, but not for T lymphocyte or NK cell development.
Height and age adjustment for cross sectional studies of lung function in children aged 6-11 years.
Authors: S Chinn, R J Rona
Journal: Thorax (1992)

BACKGROUND: No standard exists for the adjustment of lung function for height and age in children. Multiple regression should not be used on untransformed data because, for example, forced expiratory volume (FEV1), though normally distributed for height, age, and sex, has increasing standard deviation. A solution to the conflict is proposed. METHODS: Spirometry on representative samples of children aged 6.5 to 11.99 years in primary schools in England. After exclusion of children who did not provide two repeatable blows 910 white English boys and 722 girls had data on FEV1 and height. Means and standard deviations of FEV1 divided by height were plotted to determine whether logarithmic transformation of FEV1 was appropriate. Multiple regression was used to give predicted FEV1 for height and age on the transformed scale; back transformation gave predicted values in litres. Other lung function measures were analysed, and data on inner city children, children from ethnic minority groups, and Scottish children were described. RESULTS: After logarithmic (ln) transformation of FEV1 standard deviation was constant. The ratios of actual and predicted values of FEV1 were normally distributed in boys and girls. From the means and standard deviations of these distributions, and the predicted values, centiles and standard deviation scores can be calculated. CONCLUSION: The method described is valid because the assumption of stable variance for multiple regression was satisfied on the log scale and the variation of ratios of actual to predicted values on the original scale was well described by a normal distribution. The adoption of the method will lead to uniformity and greater ease of comparison of research findings.
Duration of Incubation for Serum Hepatitis And Severity of the Disease
Authors: J. Garrott Allen
Journal: JAMA (1971)

<h3>To the Editor. —</h3> Barker and Murray<sup>1</sup>have recently claimed that patients with serum hepatitis whose incubation periods were protracted were less likely to be severely ill than those whose incubation periods were relatively short. The serum samples upon which these conclusions were based were derived from experimental subjects who had received minute quantities of icterogenic serum between 1951 and 1954—minute when compared with the usual amount of blood administered as a transfusion.<sup>1-3</sup> A review of previous reports in 1970 indicated that when serum samples are altered by lyophilization, irradiation, or storage at 20 C, the mean incubation time for icterogenic plasma is lengthened.<sup>4</sup>Murray et al<sup>5</sup>found that samples of a special pool of plasma they had prepared, which normally had an attack rate of 52%, was reduced to an attack rate of 5% (or one among 20 subjects) when incubated for six months at
THE EXPERIMENTAL PRODUCTION OF COMBINATION FORMS OF VIRUS
Authors: Tamar Gotlieb, George K. Hirst
Journal: The Journal of Experimental Medicine (1954)

The simultaneous inoculation of influenza A and B strains into eggs was found to result in the formation of virus which had antigenic properties of both parent strains. The hemagglutinin of the new virus could be inhibited by both A and B antisera and the agent was also neutralized by both sera. This X particle displayed the characteristics of what we have previously called X(1). It did not reproduce itself on multiplying in the egg, but instead yielded parent types. Limiting infectious dilutions of influenza virus were studied in eggs by inoculating two different strains at once to act as markers for singly or doubly initiated infections. A base line was thus established for the frequency of single and mixed infections at virus dosages which were fractions of one ID(50). These frequencies were compared with those obtained with X viruses. X(1) virus from A-B infections did not initiate an unusual number of mixed infections at the end point. By contrast, X(1) and X(2) (M-W type) gave much higher numbers of mixed infections than did the control virus. In the discussion it is proposed (a) that doubly antigenic viruses are due to an effect known as phenotypic mixing and (b) that the ability of individual virus particles to give rise to two separate strains is due to heterozygosis or diploidy.
Therapeutic Effects of Human Mesenchymal Stem Cell–derived Microvesicles in Severe Pneumonia in Mice
Authors: Antoine Monsel, Ying-gang Zhu, Stephane Gennai, Qi Hao, Shuling Hu, Jean-Jacques Rouby, Michelle Rosenzwajg, Michael A. Matthay, Jae W. Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Microvesicles (MVs) are anuclear fragments of cells released from the endosomal compartment or shed from surface membranes. We and other investigators demonstrated that MVs released by mesenchymal stem cells (MSCs) were as effective as the cells themselves in inflammatory injuries, such as after endotoxin-induced acute lung injury. However, the therapeutic effects of MVs in an infectious model of acute lung injury remain unknown.We investigated the effects of human MSC MVs on lung inflammation, protein permeability, bacterial clearance, and survival after severe bacterial pneumonia.We tested the effects of MVs derived from human MSCs on Escherichia coli pneumonia in mice. We also studied the interactions between MVs and human monocytes and human alveolar epithelial type 2 cells.Administration of MVs derived from human MSCs improved survival in part through keratinocyte growth factor secretion and decreased the influx of inflammatory cells, cytokines, protein, and bacteria in mice injured with bacterial pneumonia. In primary cultures of human monocytes or alveolar type 2 cells, the uptake of MVs was mediated by CD44 receptors, which were essential for the therapeutic effects. MVs enhanced monocyte phagocytosis of bacteria while decreasing inflammatory cytokine secretion and increased intracellular ATP levels in injured alveolar epithelial type 2 cells. Prestimulation of MSCs with a toll-like receptor 3 agonist further enhanced the therapeutic effects of the released MVs.MVs derived from human MSCs were as effective as the parent stem cells in severe bacterial pneumonia.
Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: a population-based study, 2004–2007
Authors: Sarah Walters, Camille Maringe, Michel P Coleman, Michael D Peake, John Butler, Nicholas Young, Stefan Bergström, Louise Hanna, Erik Jakobsen, Karl Kölbeck, Stein Sundstrøm, Gerda Engholm, Anna Gavin, Marianne L Gjerstorff, Juanita Hatcher, Tom Børge Johannesen, Karen M Linklater, Colleen E McGahan, John Steward, Elizabeth Tracey, Donna Turner, Michael A Richards, Bernard Rachet
Journal: Thorax (2013)

<h3>Background</h3> The authors consider whether differences in stage at diagnosis could explain the variation in lung cancer survival between six developed countries in 2004–2007. <h3>Methods</h3> Routinely collected population-based data were obtained on all adults (15–99 years) diagnosed with lung cancer in 2004–2007 and registered in regional and national cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK. Stage data for 57 352 patients were consolidated from various classification systems. Flexible parametric hazard models on the log cumulative scale were used to estimate net survival at 1 year and the excess hazard up to 18 months after diagnosis. <h3>Results</h3> Age-standardised 1-year net survival from non-small cell lung cancer ranged from 30% (UK) to 46% (Sweden). Patients in the UK and Denmark had lower survival than elsewhere, partly because of a more adverse stage distribution. However, there were also wide international differences in stage-specific survival. Net survival from TNM stage I non-small cell lung cancer was 16% lower in the UK than in Sweden, and for TNM stage IV disease survival was 10% lower. Similar patterns were found for small cell lung cancer. <h3>Conclusions</h3> There are comparability issues when using population-based data but, even given these constraints, this study shows that, while differences in stage at diagnosis explain some of the international variation in overall lung cancer survival, wide disparities in stage-specific survival exist, suggesting that other factors are also important such as differences in treatment. Stage should be included in international cancer survival studies and the comparability of population-based data should be improved.
Necrotic inflammatory reaction induced by muramyl dipeptide in guinea pigs sensitized by tubercle bacilli.
Authors: S Nagao, A Tanaka
Journal: The Journal of Experimental Medicine (1985)

In the course of studies aimed at determining whether MDP was antigenic or not, a hitherto unreported phenomenon was noticed. Injection (a provocative injection) of muramyl dipeptide (MDP) caused severe inflammation, with hemorrhage and necrosis in the footpads of guinea pigs, where tubercle bacilli in water-oil emulsion (a preparatory injection) had been injected 3-8 wk earlier. Sometimes the reaction was accompanied by generalized and fatal shock. Several related substances were tested, and only a combination of tubercle bacilli, or MDP plus proteins as the preparatory injection, and MDP as the provocative injection was found to induce this inflammatory necrotic reaction. Development of delayed hypersensitivity to protein antigens may be important for priming, but MDP and not the protein antigens provoked the reaction. This reaction was, so far, only observed in guinea pigs. Although this reaction appears to be similar to the Shwartzman reaction, the two reactions were found to differ from each other in several important points.
Development of Spontaneous Autoimmune Peripheral Polyneuropathy in B7-2–Deficient Nod Mice
Authors: Benoît Salomon, Lesley Rhee, Helene Bour-Jordan, Honor Hsin, Anthony Montag, Betty Soliven, Jennifer Arcella, Ann M. Girvin, Stephen D. Miller, Jeffrey A. Bluestone
Journal: The Journal of Experimental Medicine (2001)

An increasing number of studies have documented the central role of T cell costimulation in autoimmunity. Here we show that the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain, deficient in B7-2 costimulation, is protected from diabetes but develops a spontaneous autoimmune peripheral polyneuropathy. All the female and one third of the male mice exhibited limb paralysis with histologic and electrophysiologic evidence of severe demyelination in the peripheral nerves beginning at 20 wk of age. No central nervous system lesions were apparent. The peripheral nerve tissue was infiltrated with dendritic cells, CD4+, and CD8+ T cells. Finally, CD4+ T cells isolated from affected animals induced the disease in NOD.SCID mice. Thus, the B7-2–deficient NOD mouse constitutes the first model of a spontaneous autoimmune disease of the peripheral nervous system, which has many similarities to the human disease, chronic inflammatory demyelinating polyneuropathy (CIDP). This model demonstrates that NOD mice have “cryptic” autoimmune defects that can polarize toward the nervous tissue after the selective disruption of CD28/B7-2 costimulatory pathway.
Salivary gland ultrasonography: can it be an alternative to sialography as an imaging modality for Sjogren's syndrome?
Authors: Y. Takagi, Y. Kimura, H. Nakamura, M. Sasaki, K. Eguchi, T. Nakamura
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objectives</h3> Salivary ultrasonography (US) was evaluated as an alternative imaging modality to sialography for Sjögren9s syndrome (SS). <h3>Methods</h3> Parotid sialography and parotid and submandibular US were performed in 360 patients (188 with SS and 172 non-SS) who were suspected of SS and had fulfilled the American-European criteria (AEC) for SS or had received ≥3 of the objective examinations that were considered minimal requirements for classifying non-SS and had undergone both the imaging examinations. The glands were considered positive for SS if they exhibited peripheral sialoectatic changes on sialography and/or hypoechoic areas, echogenic streaks and/or irregular gland margins on US. The images obtained were independently rated as SS-positive or SS-negative by three radiologists in a blind fashion and the final decision was made by consensus. Interobserver and intermodality agreement was evaluated using κ values for sialography and parotid and/or submandibular US. <h3>Results</h3> Average κ values for the interobserver agreement were 0.81, 0.80 and 0.82 in sialography, parotid and submandibular US, respectively, indicating very good or good agreement. The κ value for intermodality agreement between sialography and parotid US was 0.81 and between sialography and submandibular US was 0.76, indicating very good and good agreement, respectively. The diagnostic ability of parotid US was significantly lower than that of sialography (p&lt;0.001, McNemar test). However, the diagnostic ability of submandibular US was comparable to that of sialography (p=0.153). <h3>Conclusions</h3> Submandibular US is a promising technique that can be used as a practical alternative to sialography in the classification of SS.
Unwarranted Assumptions about Children's Testimonial Accuracy
Authors: Stephen J. Ceci, Sarah Kulkofsky, J. Zoe Klemfuss, Charlotte D. Sweeney, Maggie Bruck
Journal: Annual Review of Clinical Psychology (2007)

We examine eight unwarranted assumptions made by expert witnesses, forensic interviewers, and legal scholars about the reliability of children's eyewitness reports. The first four assumptions modify some central beliefs about the nature of suggestive interviews, age-related differences in resistance to suggestion, and thresholds necessary to produce tainted reports. The fifth unwarranted assumption involves the influence of both individual and interviewer factors in determining children's suggestibility. The sixth unwarranted assumption concerns the claim that suggested reports are detectable. The seventh unwarranted assumption concerns new findings about how children deny, disclose, and/or recant their abuse. Finally, we examine unwarranted statements about the value of science to the forensic arena. It is important not only for researchers but also expert witnesses and court-appointed psychologists to be aware of these unwarranted assumptions.
Telomerase Inhibition Potentiates the Effects of Genotoxic Agents in Breast and Colorectal Cancer Cells in a Cell Cycle–Specific Manner
Authors: Raina A. Tamakawa, Helen B. Fleisig, Judy M.Y. Wong
Journal: Cancer Research (2010)

Previous studies have shown that telomerase facilitates DNA-damage repair and cell survival following stress. It is not clear how telomerase promotes DNA repair, or whether short-term telomerase inhibition, combined with genotoxic stress, can be exploited for cancer therapy. Here, we show that transient inhibition of telomerase activity by the specific inhibitor, GRN163L, increases the cytotoxicity of some, but not all, DNA-damaging agents. Such synergistic inhibition of growth requires the use of DNA-damaging agents that are toxic in the S/G(2) phase of the cell cycle. Notably, inhibition of Ataxia Telangiectasia Mutated (ATM) kinase, together with telomerase inhibition, synergistically increases the cytotoxicity induced by the G(2)-specific topoisomerase II inhibitor etoposide. By varying the timing of telomerase inhibition, relative to the timing of DNA damage, it is apparent that the prosurvival functions of telomerase occur at early stages of DNA damage recognition and repair. Our results suggest that the protective role of telomerase in cell cycle-restricted DNA damage repair could be exploited for combined anticancer chemotherapy.
Clustering of dendritic cells, helper T lymphocytes, and histocompatible B cells during primary antibody responses in vitro.
Authors: K Inaba, M D Witmer, R M Steinman
Journal: The Journal of Experimental Medicine (1984)

Mouse spleen suspensions generate discrete cell clusters within 1-2 d of culture. We have isolated these clusters by velocity sedimentation to study their contribution to primary antibody responses. Clusters represent approximately 5% of the starting spleen cells and consist of 20-50% B cells, 20-50% T cells, and 10-20% dendritic cells (DC). When the cultures are stimulated with thymus-dependent antigens, like heterologous red cells or dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH), the clusters are the principal site for the development of plaque-forming cells (PFC). Noncluster fractions form few PFC and only when supplemented with fresh DC. PFC responses in all cases are antigen specific. B cells cluster only in the presence of T cells and DC (1 DC/200 B-T cell mixtures) and only after encountering specific antigen. The elimination of either DC or Lyt-1+2- T cells, with monoclonal antibody and complement, ablates B cell development into PFC. PFC responses are restored with antigen-nonspecific helper factors formed in the syngeneic mixed leukocyte reaction between DC and T cells. Since PFC to DNP-KLH do not develop de novo when B cells are exposed to antigen and helper factors, anti-DNP PFC precursors must be stimulated within clusters to become responsive to helper factors. PFC development within clusters is restricted by the major histocompatibility complex (MHC). When DC and T cells are from strain P1, then P1 but not P2 B cells develop into PFC; when DC are from strain P2 and T cells from strain P1, strain P2 B cells are selected to become PFC in clusters. The entry of B cells into clusters is itself MHC restricted, since P1 DC/T cells aggregate six times as many B cells from strain P1 as strain P2. Thus, clusters are the site in which DC, B, and T cells interact to generate PFC. One can use clusters to retrieve B cells that have been selected in an antigen-dependent, MHC-restricted fashion and to show that clustering B cells become responsive to soluble, polyclonal helper factors.
Biosimilar G-CSF Based Mobilization Of Peripheral Blood Hematopoietic Stem Cells For Autologous and Allogeneic Stem Cell Transplantation
Authors: Michael Schmitt, Amy Publicover, Kim H. Orchard, Anita Schmitt, Panagiotis Tsirigotis, Reeba Kuriakose, Arnon Nagler
Journal: Blood (2013)
Higher Rate of Obesity and Hypertension in Adolescents With Type 2 Diabetes Than in Those With Type 1 Diabetes
Authors: Hung-Yuan Li, Jung-Nan Wei, Fung-Chang Sung, Lee-Ming Chuang
Journal: Diabetes Care (2006)

We read with interest the article by Eppens et al. (1) concerning the prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes.

Because the study was clinic based and included a relatively small number of subjects with type 2 diabetes ( n = 68), we present our findings from a nationwide screening program, which was conducted between 1992 and 1997 for all schoolchildren aged 6–18 years (2). Diabetes was diagnosed in 381 boys and 454 girls …