tbuckley/cabot-search huggingface dataset:
Absence of IgD-CD27(+) memory B cell population in X-linked hyper-IgM syndrome.
Authors: K Agematsu, H Nagumo, K Shinozaki, S Hokibara, K Yasui, K Terada, N Kawamura, T Toba, S Nonoyama, H D Ochs, A Komiyama
Journal: Journal of Clinical Investigation (1998)

The present study analyzed peripheral blood B cell populations separated by IgD and CD27 expression in six males with X-linked hyper-IgM syndrome (XHIM). Costimulation of mononuclear cells from most of the patients induced no to low levels of class switching from IgM to IgG and IgA with Staphylococcus aureus Cowan strain (SAC) plus IL-2 or anti-CD40 mAb (anti-CD40) plus IL-10. Measurable levels of IgE were secreted in some of the patients after stimulation with anti-CD40 plus IL-4. Costimulation with SAC plus IL-2 plus anti-CD40 plus IL-10 yielded secretion of significant levels of IgG in addition to IgM, but not IgA. The most striking finding was that peripheral blood B cells from all of the six patients were composed of only IgD+ CD27(-) and IgD+ CD27(+) B cells; IgD- CD27(+) memory B cells were greatly decreased. IgD+ CD27(+) B cells from an XHIM patient produced IgM predominantly. Our data indicate that the low response of IgG production in XHIM patients is due to reduced numbers of IgD- CD27(+) memory B cells. However, the IgG production can be induced by stimulation of immunoglobulin receptors and CD40 in cooperation with such cytokines as IL-2 and IL-10 in vitro.
Pretreatment Tables Predicting Pathologic Stage of Locally Advanced Prostate Cancer
Authors: Steven Joniau, Martin Spahn, Alberto Briganti, Giorgio Gandaglia, Bertrand Tombal, Lorenzo Tosco, Giansilvio Marchioro, Chao-Yu Hsu, Jochen Walz, Burkhard Kneitz, Pia Bader, Detlef Frohneberg, Alessandro Tizzani, Markus Graefen, Paul van Cangh, R. Jeffrey Karnes, Francesco Montorsi, Hein van Poppel, Paolo Gontero
Journal: European Urology (2014)
Right Bundle-Branch Block Ventricular Tachycardias
Authors: Vickas V. Patel, Robert W. Rho, Edward P. Gerstenfeld, Henry H. Hsia, David J. Callans, Francis E. Marchlinski
Journal: Circulation (2004)

Identifying the septal versus lateral site of origin of ventricular tachycardia (VT) with a right bundle-branch block (RBBB)-type pattern and an R-S ratio >1 in lead V1 is difficult with the 12-lead ECG, especially in patients with prior apical infarction.We prospectively evaluated 58 patients with VT. Sixteen patients had apical infarcts (group 1), 29 had nonapical infarcts (group 2), and 13 had no heart disease (group 3). QRS complex onset to activation at the right ventricular apex (stim-RVA) was measured during left ventricular (LV) apical septal and lateral pacing, and 47 RBBB-type VTs (QRS-RVA) were localized to the septal or lateral apex by using entrainment techniques. Pacing and VT site of origin were confirmed by electroanatomic mapping. The stim-RVA time was 59+/-16 ms for septal versus 187+/-24 ms for lateral sites in group 1, P<0.001; 70+/-14 ms for septal versus 169+/-19 ms for lateral sites in group 2, P<0.001; and 42+/-15 ms for septal versus 86+/-16 ms for lateral sites in group 3, P<0.005. The QRS-RVA time was 50+/-13 ms for apical septal VTs versus 178+/-21 ms for lateral VTs in group 1, P<0.001; 71+/-17 ms for apical septal versus 157+/-20 ms for lateral VTs in group 2, P<0.001; and 32+/-12 ms for septal versus 71+/-16 ms for lateral VTs in group 3, P<0.01.The QRS-RVA differs for the VT site of origin from the LV septal versus lateral apex. These data prove useful in rapidly regionalizing the VT site of origin with a V1 R-S ratio >1, particularly in instances of an apical infarct, where surface ECG distinctions are less identifiable.
Inverse Correlation between Cyclin A1 Hypermethylation and p53 Mutation in Head and Neck Cancer Identified by Reversal of Epigenetic Silencing
Authors: Yutaka Tokumaru, Keishi Yamashita, Motonobu Osada, Shuji Nomoto, Dong-Il Sun, Yan Xiao, Mohammad Obaidul Hoque, William H. Westra, Joseph A. Califano, David Sidransky
Journal: Cancer Research (2004)

Abstract Aberrant promoter hypermethylation of tumor suppressor genes is proposed to be a common feature of primary cancer cells. We recently developed a pharmacological unmasking microarray approach to screen unknown tumor suppressor gene candidates epigenetically silenced in human cancers. In this study, we applied this method to identify such genes in head and neck squamous cell carcinoma (HNSCC). We identified 12 novel methylated genes in HNSCC cell lines, including PGP9.5, cyclin A1, G0S2, bone-morphogenetic protein 2A, MT1G, and neuromedin U, which showed frequent promoter hypermethylation in primary HNSCC (60%, 45%, 35%, 25%, 25%, and 20%, respectively). Moreover, we discovered that cyclin A1 methylation was inversely related to p53 mutational status in primary tumors (P = 0.015), and forced expression of cyclin A1 resulted in robust induction of wild-type p53 in HNSCC cell lines. Pharmacological unmasking followed by microarray analysis is a powerful tool to identify key methylated tumor suppressor genes and relevant pathways.
Thy1 (+) and (-) lung fibrosis subpopulations in LEW and F344 rats
Authors: JC McIntosh, JS Hagood, TL Richardson, JW Simecka
Journal: European Respiratory Journal (1994)

Appreciation of the potential of fibroblasts as effector cells in inflammation has led to the recognition of fibroblast subpopulations, the most stable of which are the Thy1 (+) and Thy1 (-) subpopulations in mouse lung fibroblasts. We investigated the presence of Thy1 (+) and (-) fibroblasts in rats, comparing the percentage in primary cultures from rats with different susceptibility to fibrosis, and whether the characteristics were similar in mice and rats, and between normal and fibrotic rats lungs. Using primary cultures of rat fibroblasts obtained both from normal and fibrotic lungs, we analysed the percentage of Thy1 (+) and (-) fibroblasts by fluorescence-activated cell sorter (FACS) analysis. We sorted the fibroblasts to evaluate immune region associated antigen (Ia) expression, which tends to be raised in tissues involved in inflammation, and other characteristics. We found that Thy1 (+) and (-) fibroblasts: 1) are distinct subpopulations in rat lungs; 2) are found in different proportions in rat strains with different propensity towards lung fibrosis; and 3) have similar but not identical characteristics in mice and rats. We also found that bleomycin-induced fibrosis increases the percentage of Ia expression in Thy1 (-), but not Thy1 (+) fibroblasts. The presence of these stable fibroblast supopulations in multiple species, and the fact that these fibroblasts differ in their response to a fibrosing agent, suggests the importance of considering fibroblast subpopulations in development and disease.
Osteoporosis in Patients With Schizophrenia
Authors: Martina Hummer, Peter Malik, Rudolf W. Gasser, Alex Hofer, Georg Kemmler, Roy Cesar Moncayo Naveda, Maria A. Rettenbacher, W. Wolfgang Fleischhacker
Journal: American Journal of Psychiatry (2004)

Osteoporosis is regularly mentioned as a possible consequence of treatment with prolactin-increasing antipsychotic medications, but little is known about the prevalence and the degree of loss of bone mineral density in patients suffering from schizophrenia. The authors' goals were to investigate the association between schizophrenia and a decrease in bone mineral density and to get more insight into potential underlying pathophysiological mechanisms.In a cross-sectional study, the authors used dual x-ray absorptiometry to determine bone mineral density of 75 inpatients and outpatients suffering from schizophrenia. All patients had been treated with antipsychotics for at least 1 year, and only patients between the ages of 19 and 50 were studied to exclude patients with age-related idiopathic osteoporosis.In men but not women with schizophrenia, bone mineral density was significantly lower than normal in the lumbar region. A comparison of loss of bone mineral density in male and female patients showed significant differences between the sexes. Bone mineral density showed a negative correlation with negative symptoms and Positive and Negative Syndrome Scale total score and a positive correlation with 25-hydroxy-vitamin D3 levels and body mass index in male patients. In female patients, a positive correlation between body mass index and bone mineral density was found. Exposure to prolactin-increasing antipsychotics was not related to bone mineral density.The male patients with schizophrenia in this study suffered from low bone density. This finding as well as other reports lend support to directing more attention to bone metabolism in patients with schizophrenia, although there is no universally accepted screening policy to identify individuals at high risk for osteoporosis.
Nonmelanoma Cutaneous Head and Neck Cancer and Merkel Cell Carcinoma: Current Concepts, Advances, and Controversies
Authors: Sandro V. Porceddu, Michael J. Veness, Alexander Guminski
Journal: Journal of Clinical Oncology (2015)

Nonmelanoma skin cancer (NMSC) is the most common cancer worldwide and the most frequently observed malignancy in whites. Approximately 75% to 80% are basal cell carcinomas and 20% to 25% are squamous cell carcinomas. Incidence is increasing, partly reflecting an ageing population, and NMSC is more commonly seen in men. The predominant causative agent is ultraviolet solar radiation exposure, with the majority of cases occurring on the head and neck. Surgical excision is typically the treatment of choice, providing histopathologic information, high cure rates, and acceptable cosmetic and functional outcomes. Radiation therapy is reserved for cases where surgery is not the preferred choice or for high-risk cases where adjuvant therapy is recommended. Although overall mortality rates are low, patients with complex cases such as those with immunosuppression should be considered for management within multidisciplinary tumor boards. In contrast, Merkel cell carcinoma is a rare and aggressive malignancy, frequently arising on the head and neck in older whites, with a poorer prognosis. This article focuses on the current evidence guiding practice, recent advances, and areas of controversy in NMSC and Merkel cell carcinoma of the head and neck.
The Multifaceted Functions of Neutrophils
Authors: Tanya N. Mayadas, Xavier Cullere, Clifford A. Lowell
Journal: Annual Review of Pathology Mechanisms of Disease (2013)

Neutrophils and neutrophil-like cells are the major pathogen-fighting immune cells in organisms ranging from slime molds to mammals. Central to their function is their ability to be recruited to sites of infection, to recognize and phagocytose microbes, and then to kill pathogens through a combination of cytotoxic mechanisms. These include the production of reactive oxygen species, the release of antimicrobial peptides, and the recently discovered expulsion of their nuclear contents to form neutrophil extracellular traps. Here we discuss these primordial neutrophil functions, which also play key roles in tissue injury, by providing details of neutrophil cytotoxic functions and congenital disorders of neutrophils. In addition, we present more recent evidence that interactions between neutrophils and adaptive immune cells establish a feed-forward mechanism that amplifies pathologic inflammation. These newly appreciated contributions of neutrophils are described in the setting of several inflammatory and autoimmune diseases.
Pulmonary artery pressure--flow plots in hyperoxic and in hypoxic dogs: effects of prostaglandin E1
Authors: M Leeman, P Lejeune, C Melot, R Naeije
Journal: European Respiratory Journal (1988)

The effects of prostaglandin E1 on mean pulmonary artery pressure (Ppa):cardiac index (Q) relationships were investigated in eight anaesthetized dogs, ventilated in hyperoxia (fraction of inspired oxygen (FiO2) 0.4) and in hypoxia (FiO2 0.1). Cardiac output was increased by opening an arterio-venous femoral bypass or reduced by stepwise inflations of a balloon in the inferior vena cava. Five-point Ppa:Q relationships were found to be linear in all experimental conditions. Hypoxia increased Ppa over the entire range of Q studied (1-5l.min-1.m-2). Prostaglandin E1 0.4 microgram.kg-1.min-1 intravenously decreased hyperoxic Ppa for Q ranging from 3-5 l.min-1.m-2, hypoxic Ppa for Q ranging from 2-5 l.min-1.m-2 and attenuated hypoxia-induced increases in Ppa. These results show that prostaglandin E1 is a pulmonary vasodilator in both hyperoxic and hypoxic conditions. At the dose of 0.4 microgram.kg-1, prostaglandin E1 partially inhibits hypoxic pulmonary vasoconstriction.
Abstract A21: Thrombin-processed Ecrg4 recruits myeloid cells and induces anti-tumorigenic inflammation
Authors: Jisook Lee, Alexandra Borboa, Andrew Baird, Brian Eliceiri
Journal: Cancer Research (2015)

Abstract Myeloid cells regulate tumor angiogenesis and promote tumor invasion, yet few strategies exist to exploit their presence to reverse the overall immunosuppressive tumor microenvironment. Based on bioinformatic mining of sentinel genes encoding biologically active peptides, we have recently identified Ecrg4 (Esophageal Cancer-Related Gene 4), as a novel secreted pro-inflammatory mediator of macrophage activation. While higher Ecrg4 expression levels correlate with improved survival in cancers of the esophagus, prostate and breast, indicating a role as a candidate tumor suppressor gene, we have demonstrated that the biological activity of Ecrg4 in cancer functions through a paracrine mechanism, in which Ecrg4 regulates myeloid cells in brain tumors. Moreover, mutational analysis reveals that the biological activity of Ecrg4 is dependent on a thrombin-processing site at the C-terminus, inducing monocyte invasion in vivo and in vitro, demonstrating its role as a novel chemoattractant. Here we establish Ecrg4 as a thrombin-processed chemoattractant using subcutaneous tumor models. Ecrg4 gene delivery or Ecrg4 (133-148) peptide administration to tumor reduced melanoma progression through mobilization and activation of myeloid cells to tumor site. Furthermore, in Ecrg4-knockout mice, myeloid cell recruitment is impaired, leading to increased tumor burden. Together, these results identify Ecrg4 as a paracrine factor that is chemotactic for monocytes, with translational potential as an anti-tumor therapeutic. Citation Format: Jisook Lee, Alexandra Borboa, Andrew Baird, Brian Eliceiri. Thrombin-processed Ecrg4 recruits myeloid cells and induces anti-tumorigenic inflammation. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A21. doi:10.1158/1538-7445.CHTME14-A21
Cardiac Progenitor Cell Cycling Stimulated by Pim-1 Kinase
Authors: Christopher T. Cottage, Brandi Bailey, Kimberlee M. Fischer, Daniele Avitabile, Brett Collins, Savilla Tuck, Pearl Quijada, Natalie Gude, Roberto Alvarez, John Muraski, Mark A. Sussman
Journal: Circulation Research (2010)

Cardioprotective effects of Pim-1 kinase have been previously reported but the underlying mechanistic basis may involve a combination of cellular and molecular mechanisms that remain unresolved. The elucidation of the mechanistic basis for Pim-1 mediated cardioprotection provides important insights for designing therapeutic interventional strategies to treat heart disease.Effects of cardiac-specific Pim-1 kinase expression on the cardiac progenitor cell (CPC) population were examined to determine whether Pim-1 mediates beneficial effects through augmenting CPC activity.Transgenic mice created with cardiac-specific Pim-1 overexpression (Pim-wt) exhibit enhanced Pim-1 expression in both cardiomyocytes and CPCs, both of which show increased proliferative activity assessed using 5-bromodeoxyuridine (BrdU), Ki-67, and c-Myc relative to nontransgenic controls. However, the total number of CPCs was not increased in the Pim-wt hearts during normal postnatal growth or after infarction challenge. These results suggest that Pim-1 overexpression leads to asymmetric division resulting in maintenance of the CPC population. Localization and quantitation of cell fate determinants Numb and alpha-adaptin by confocal microscopy were used to assess frequency of asymmetric division in the CPC population. Polarization of Numb in mitotic phospho-histone positive cells demonstrates asymmetric division in 65% of the CPC population in hearts of Pim-wt mice versus 26% in nontransgenic hearts after infarction challenge. Similarly, Pim-wt hearts had fewer cells with uniform alpha-adaptin staining indicative of symmetrically dividing CPCs, with 36% of the CPCs versus 73% in nontransgenic sections.These findings define a mechanistic basis for enhanced myocardial regeneration in transgenic mice overexpressing Pim-1 kinase.
Problem Doctors: Is There a System-Level Solution?
Authors: Lucian L. Leape, John A. Fromson
Journal: Annals of Internal Medicine (2006)

Physician performance failures are not rare and pose substantial threats to patient welfare and safety. Few hospitals respond to such failures promptly or effectively. Failure to ensure the quality and safety of the performance of colleagues is a breach of medicine's fiduciary responsibility to the public. A major reason for this deficiency is the hospitals' lack of formal systems to monitor physician performance and to identify and correct shortcomings. To develop and implement these systems, hospitals need better performance measures and substantial expansion of external programs for assessment and remediation. This is a task well beyond the capacities of individual hospitals; a national effort is required. The authors call on the Federation of State Medical Boards, the American Board of Medical Specialties, and the Joint Commission on Accreditation of Healthcare Organizations (organizations that already bear a fiduciary responsibility for ensuring safe, competent care) to collaborate on developing better methods for measuring performance and to expand programs for helping practitioners who are deficient.
Reply to Pascal Mouracade's Letter to the Editor re: R. Houston Thompson, Tom Atwell, Grant Schmit, et al. Comparison of Partial Nephrectomy and Percutaneous Ablation for cT1 Renal Masses. Eur Urol 2015;67:252–9
Authors: R. Houston Thompson, Tom Atwell, Grant Schmit, Christine M. Lohse, A. Nicholas Kurup, Adam Weisbrod, Sarah P. Psutka, Suzanne B. Stewart, Matthew R. Callstrom, John C. Cheville, Stephen A. Boorjian, Bradley C. Leibovich
Journal: European Urology (2015)
Conservation of the lipooligosaccharide synthesis locus lgt among strains of Neisseria gonorrhoeae: requirement for lgtE in synthesis of the 2C7 epitope and of the beta chain of strain 15253.
Authors: A L Erwin, P A Haynes, P A Rice, E C Gotschlich
Journal: The Journal of Experimental Medicine (1996)

The present study was undertaken to examine the extent to which the lgt locus varies among strains of gonococci. This locus encodes five glycosyl transferases involved in the synthesis of the lipooligosaccharide (LOS) of Neisseria gonorrhoeae. We examined seven gonococcal strains and found that the structure of the lgt locus is conserved among six of these strains. The locus is strikingly altered in strain 15253. This is one of the few strains where extensive structural analysis of its LOS is available, and therefore, we defined the altered lgt locus and focused on the reactivity of mAB 2C7. We found that strain 15253 contains only two lgt genes, lgtA and lgtE. As in F62, lgtA encodes a GlcNAc transferase and is subject to phase variation. In addition, by analysis of deletion mutants, we found that lgtE, which encodes a galactosyl transferase that is required for elongating the alpha-chain, is also necessary for completing the beta chain.
Evolution of the Australian Lungfish (Neoceratodus forsteri) Genome: A Major Role for CR1 and L2 LINE Elements
Authors: C. J. Metcalfe, J. Filee, I. Germon, J. Joss, D. Casane
Journal: Molecular Biology and Evolution (2012)

Haploid genomes greater than 25,000 Mb are rare, within the animals only the lungfish and some of the salamanders and crustaceans are known to have genomes this large. There is very little data on the structure of genomes this size. It is known, however, that for animal genomes up to 3,000 Mb, there is in general a good correlation between genome size and the percent of the genome composed of repetitive sequence and that this repetitive component is highly dynamic. In this study, we sampled the Australian lungfish genome using three mini-genomic libraries and found that with very little sequence, the results converged on an estimate of 40% of the genome being composed of recognizable transposable elements (TEs), chiefly from the CR1 and L2 long interspersed nuclear element clades. We further characterized the CR1 and L2 elements in the lungfish genome and show that although most CR1 elements probably represent recent amplifications, the L2 elements are more diverse and are more likely the result of a series of amplifications. We suggest that our sampling method has probably underestimated the recognizable TE content. However, on the basis of the most likely sources of error, we suggest that this very large genome is not largely composed of recently amplified, undetected TEs but may instead include a large component of older degenerate TEs. Based on these estimates, and on Thomson's (Thomson K. 1972. An attempt to reconstruct evolutionary changes in the cellular DNA content of lungfish. J Exp Zool. 180:363–372) inference that in the lineage leading to the extant Australian lungfish, there was massive increase in genome size between 350 and 200 mya, after which the size of the genome changed little, we speculate that the very large Australian lungfish genome may be the result of a massive amplification of TEs followed by a long period with a very low rate of sequence removal and some ongoing TE activity.