tbuckley/cabot-search huggingface dataset:
Two stages of B-cell memory development with different T-cell requirements.
Authors: K Okumura, C M Metzler, T T Tsu, L A Herzenberg, L A Herzenberg
Journal: The Journal of Experimental Medicine (1976)

We present evidence here for two stages in B-memory cell development, the first of which is T independent and the second T dependent. For these studies, we use a new type of T-deficient mouse (allotype suppressed) which specifically lacks T-helper activity (Th) for a subset of memory B cells responsible for approximately 10% of the overall IgG antibody response. We have shown elsewhere that these mice (SJL X BALB/c hybrids suppressed for Ig-1b) lack Th capable of helping Ig-1b memory cells, although they have normal Th activity for all other IgG memory B cells. This selective Th deficiency allows study of the effects of T depletion on memory development and avidity maturation of one population of B cells under conditions where the bulk of the immune response in the animal is proceeding normally, thus obviating environmental problems due to secondary effects of T depletion. With this sytem, we show that after a single priming dose of 2,4-dinitrophenyl-keyhole limpet hemocyanin, the memory B-cell pool in suppressed and nonsuppressed donors is indistinguishable with respect to magnitude and avidity of the response for all IgG antibodies produced, including Ig-1b antibody, despite the fact that expression of Ig-1b memory cells is prevented in intact Ig-1b-suppressed mice by the absence of Th capbale of cooperating with these memory cells. We have shown elsewhere that virtually all of the Ig-1b memory is carried by Ig-1b bearing cells. In contrast with the lack of suppressor T-cell effect on initial Ig-1b memory cell development, our data show that continued Ig-1b memory development is selectively impaired in suppressed mice. When primed mice are boosted repeatedly with the priming antigen, the average avidity of most of the IgG memory cells increases over 100-fold while there is no avidity increase in the Ig-1b component. To explain these data, we suggest that the development of high avidity memory occurs in two stages. The first stage, which occurs as a result of primary antigenic exposure, is the creation of a pool of IgG-bearing memory cells with a relatively low average avidity for the antigen. The appearance of these first stage memory cells does not require help from (post-thymic) Th, although Th are required for the expression of these memory cells (antibody production). The second stage of B-memory development requires both further antigenic stimulation and B-memory cell interaction with competent Th. This is a continuing process in which the number of memory cells in the pool remains relatively constant but the average avidity of these cells increases with continued antigenic exposure.
Diagnosis of Bilateral Giant Adrenal Myelolipoma
Authors: Dominik Ketelsen, Claus Hann von Weyhern, Marius Horger
Journal: Journal of Clinical Oncology (2010)

A 33-year-old obese woman presented with a retroperitonealmassasanincidentalﬁndingduringherniasurgery.Aphysicalexam-inationrevealednopathologicﬁnding.Obesitypreventedpalpationofany abdominal mass. At the time of presentation to our hospital atEberhard-Karls-University(Tu¨bingen,Germany),laboratoryparam-eters were at normal levels. A computed tomography scan showedbilateral giant adrenal tumors with predominantly fatty regions (Fig1A;straightwhitearrows)interspersedwithsolid,septa-liketissue(Fig1A; curved white arrow) demonstrating mild enhancement after in-travenouscontrastadministration.Themasseswereencapsulatedandmeasured19.1 10.5 22.6cmattheleftand12.3 8.7 19.3cmat the right side, compressing retroperitoneal vessels. The tumor waswell circumscribed and extended to the surrounding tissue withoutinvasion. The suspected diagnosis of bilateral adrenal myelolipomaswas histologically conﬁrmed after a computed tomography–guidedbiopsy. The microscopic analysis of biopsy samples revealed adipo-cytes with clear cytoplasm, interspersed with cells of hematopoiesis.One half of the cells were erythroid nests with dense blue nuclei (Fig1B,whitestar).Theothercellswereprimarilyofmyeloidlineagewithmaturation to segmented granulocytes (Fig 1B; white arrow). Onemultilobulatedmegakaryocytewasalsopresentinthebonemarrow–likespecimen.Giventheabsenceofclinicalsymptoms,thetreatmentstrategychosenwasawatchandwaitregimen.First described in 1905, adrenal myelolipomas are rare, hor-monally inactive, benign tumors that are composed of mature fattissue and hematopoietic elements.
A functional polymorphism of TIR-domain-containing adaptor protein is not associated with axial spondyloarthritis
Authors: T Cantaert, M A Stone, M t. Borg, R Mogg, N De Vries, A G Wilson, P P Tak, D Baeten
Journal: Annals of the Rheumatic Diseases (2007)

A genetic variant of the toll-like receptor (TLR)2/4 adaptor protein TIRAP (single nucleotide polymorphism (SNP) C539T) was identified in a UK and in several African populations. The heterozygous genotype of this SNP has been associated with protection from severe infections. This allele results in an attenuated response to bacterial pathogens. As an exaggerated innate immune response to pathogens has been implicated in spondyloarthritis (SpA) pathogenesis, we analysed if the heterozygous C/T genotype was underrepresented in axial SpA compared with healthy controls.204 patients with axial SpA and 175 population-matched controls were included. SNP C539T was determined with a sequence-specific polymerase chain reaction and direct sequencing.The frequency of the haplotypes was similar in cases and controls (87% for C and 13% for T in both groups). The C/T genotype, which attenuates TLR signalling, was not underrepresented in cases versus controls (19% in controls vs 24% in cases, p = 0.44). The T/T genotype, was slightly lower in cases than in controls, although this was not significant (3.4% in controls vs 1% in cases, p = 0.15). Within the cases, there were no differences in disease phenotype or activity between patients with the C/C or C/T genotype.This study did not show significant associations of SNP S180L of the TLR2/4 adaptor protein TIRAP with axial SpA.
Etiology of Community-Acquired Pneumonia:
Authors: MAURICIO RUIZ, SANTIAGO EWIG, MARIA ANGELES MARCOS, JOSE ANTONIO MARTINEZ, FRANCISCO ARANCIBIA, JOSEP MENSA, ANTONI TORRES
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The aim of this study was to determine the etiology of community-acquired pneumonia (CAP) and the impact of age, comorbidity, and severity on microbial etiologies of such pneumonia. Overall, 395 consecutive patients with CAP were studied prospectively during a 15-mo period. Regular microbial investigation included examination of sputum, blood culture, and serology. Sampling of pleural fluid, transthoracic puncture, tracheobronchial aspiration, and protected specimen brush (PSB) sampling were performed in selected patients. The microbial etiology was determined in 182 of 395 (46%) cases, and 227 pathogens were detected. The five most frequent pathogens were Streptococcus pneumoniae (65 patients [29%]), Haemophilus influenzae (25 patients [11%]), Influenza virus A and B (23 patients [10%]), Legionella sp. (17 patients [8%]), and Chlamydia pneumoniae (15 patients [7%]). Gram-negative enteric bacilli (GNEB) accounted for 13 cases (6%) and Pseudomonas aeruginosa for 12 cases of pneumonia (5%). Patients aged < 60 yr were at risk for an “atypical” bacterial etiology (odds ratio [OR]: 2.3; 95% confidence interval [CI]: 1.2 to 4.5), especially Mycoplasma pneumoniae (OR: 5.3; 95% CI: 1.7 to 16.8). Comorbid pulmonary, hepatic, and central nervous illnesses, as well as current cigarette smoking and alcohol abuse, were all associated with distinct etiologic patterns. Pneumonia requiring admission to the intensive care unit was independently associated with the pathogens S. pneumoniae (OR: 2.5; 95% CI: 1.3 to 4.7), gram-negative enteric bacilli, and P. aeruginosa (OR: 2.5; 95% CI: 0.99 to 6.5). Clinical and radiographic features of “typical” pneumonia were neither sensitive nor specific for the differentiation of pneumococcal and nonpneumococcal etiologies. These results support a management approach based on the associations between etiology and age, comorbidity, and severity, instead of the traditional syndromic approach to CAP.
The Nm23-H1 Gene Acts as a Migration Suppressor in Gastric Lymphoma
Authors: Dae Young Cheung, Hye Kang Kim, Hyun Jin Kim, Hyung Jun Cho, Jae Kwang Kim, Jin Il Kim, Soo-Heon Park, Seong Jin Lee, Joon Han Jeon
Journal: Annals of Oncology (2013)
A randomized trial of rescue angioplasty versus a conservative approach for failed fibrinolysis in ST-segment elevation myocardial infarction
Authors: Andrew G.C. Sutton, Philip G. Campbell, Richard Graham, Dallas J.A. Price, Janine C. Gray, Ever D. Grech, James A. Hall, Alun A. Harcombe, Robert A. Wright, Roger H. Smith, Jerry J. Murphy, Ananthaiah Shyam-Sundar, Michael J. Stewart, Adrian Davies, Nicholas J. Linker, Mark A. de Belder
Journal: Journal of the American College of Cardiology (2004)
Trephine biopsy of the lung and pleura
Authors: S. J. Steel, D. P. Winstanley
Journal: Thorax (1969)

During the last five years 140 biopsies of the lung or pleura have been performed with a high-speed air-drill. A specially designed trephine, 2·1 mm. in bore, proved effective in obtaining adequate specimens from patients with diffuse lung lesions. With this method 111 out of 119 (93%) consecutive lung biopsies were successful in producing specimens of lung tissue for histological examination and 101 (85%) of these biopsies were diagnostically significant. Conditions such as sarcoidosis, berylliosis, alveolar proteinosis, polyarteritis nodosa, asbestosis, and diffuse interstitial pulmonary fibrosis were conclusively diagnosed. Complications were not serious and the commonest, pneumothorax, which occurred in 26% of the lung biopsies, was usually asymptomatic. The procedure is rapid and painless and breath-holding is unnecessary. It is performed under local anaesthesia and can be repeated, if required, thus having many advantages over biopsy by open thoracotomy. However, full thoracic surgical cover should be available. Indications include diffuse and localized lesions of the lung or pleura where a definitive diagnosis is required for the purpose of treatment, prognosis, or a claim for industrial compensation.
The unfolded protein response sensor IRE1α is required at 2 distinct steps in B cell lymphopoiesis
Authors: Kezhong Zhang, Hetty N. Wong, Benbo Song, Corey N. Miller, Donalyn Scheuner, Randal J. Kaufman
Journal: Journal of Clinical Investigation (2005)

B lymphocyte differentiation is coordinated with the induction of high-level Ig secretion and expansion of the secretory pathway. Upon accumulation of unfolded proteins in the lumen of the ER, cells activate an intracellular signaling pathway termed the unfolded protein response (UPR). Two major proximal sensors of the UPR are inositol-requiring enzyme 1α (IRE1α), an ER transmembrane protein kinase/endoribonuclease, and ER-resident eukaryotic translation initiation factor 2α (eIF2α) kinase (PERK). To elucidate whether the UPR plays an important role in lymphopoiesis, we carried out reconstitution of recombinase-activating gene 2–deficient (rag2–/–) mice with hematopoietic cells defective in either IRE1α- or PERK-mediated signaling. IRE1α-deficient (ire1α–/–) HSCs can proliferate and give rise to pro–B cells that home to bone marrow. However, IRE1α, but not its catalytic activities, is required for Ig gene rearrangement and production of B cell receptors (BCRs). Analysis of rag2–/– mice transplanted with IRE1α trans-dominant-negative bone marrow cells demonstrated an additional requirement for IRE1α in B lymphopoiesis: both the IRE1α kinase and RNase catalytic activities are required to splice the mRNA encoding X-box–binding protein 1 (XBP1) for terminal differentiation of mature B cells into antibody-secreting plasma cells. Furthermore, UPR-mediated translational control through eIF2α phosphorylation is not required for B lymphocyte maturation and/or plasma cell differentiation. These results suggest specific requirements of the IRE1α-mediated UPR subpathway in the early and late stages of B lymphopoiesis.
Rate of change of FEV1 and VC in adults with chronic airflow obstruction
Authors: Andrew Robson, Alastair Innes
Journal: European Respiratory Journal (2012)

We have investigated the rate of change in post-bronchodilator FEV 1  and VC in patients with chronic airflow obstruction by retrospective analysis of data in our clinical database. One thousand and forty-four patients (633 females) fulfilled the study criteria, namely two sets of measurements with a minimum of six calendar months between measurements. Measurements of FEV 1  and VC were made before and 20 minutes after administration of 2.5 mg nebulised salbutamol. Only patients with an FEV 1 /VC ratio below the lower limit of normal after administration of 2.5 mg nebulised salbutamol were included in the study. Rate of change in FEV 1  was calculated in litres/year. Smoking status (smoker, ex-smoker or non-smoker) was recorded at each visit, but the number of cigarettes smoked was not recorded. Patients were only identified as smokers if the same status was recorded at both measurements. The rate of change in post salbutamol FEV 1  and VC in all patients and in the subgroup of smokers are shown in Table 1. Values shown are mean ± SD.  The rate of change in FEV 1  and VC in patients is significantly higher in males when compared to females. Males who continue to smoke have a greater rate of change in both FEV 1  and VC than females who smoke. Further investigation into these gender differences is warranted.
Claudin Proteins in Human Cancer: Promising New Targets for Diagnosis and Therapy
Authors: Patrice J. Morin
Journal: Cancer Research (2005)

Abstract The tight junction proteins claudins are abnormally regulated in several human cancers. In particular, claudin-3 and claudin-4 are frequently overexpressed in several neoplasias, including ovarian, breast, pancreatic, and prostate cancers. Although the exact roles of these proteins in tumorigenesis are still being uncovered, it is clear that they represent promising targets for cancer detection, diagnosis, and therapy.
The American Diabetes Association Should Be a Leader in Reducing Medication Errors
Authors: Daniel J. Crowe
Journal: Diabetes Care (2001)

The 1999 publication of the Institute of Medicine’s (IOM’s) review of medical errors, To Err is Human : Building a Safer Health System (1), along with the publication of Michael Cohen’s book, Medical Errors (2), highlighted the impact that medical errors have on the U.S. health care system and the potential for high morbidity and possible fatal outcome for the individual patient (7,000+ deaths per year from medication errors). Throughout the country, health care providers, hospitals, and delivery systems are making elimination of medication-related errors a top priority, with strong support from major employers and …
The Receptor Tyrosine Kinase EPHB4 Has Tumor Suppressor Activities in Intestinal Tumorigenesis
Authors: Higinio Dopeso, Silvia Mateo-Lozano, Rocco Mazzolini, Paulo Rodrigues, Laura Lagares-Tena, Julian Ceron, Jordi Romero, Marielle Esteves, Stefania Landolfi, Javier Hernández-Losa, Julio Castaño, Andrew J. Wilson, Santiago Ramon y Cajal, John M. Mariadason, Simo Schwartz, Diego Arango
Journal: Cancer Research (2009)

Abstract Colorectal cancer is the second cause of cancer-related death in the western world, and although the genetic and molecular mechanisms involved in the initiation and progression of these tumors are among the best characterized, there are significant gaps in our understanding of this disease. The role of EPHB signaling in colorectal cancer has only recently been realized. Here, we use animal models to investigate the role of EphB4 in intestinal tumorigenesis. Modulation of EPHB4 levels in colon cancer cell lines resulted in significant differences in tumor growth in a xenograft model, with low levels of EPHB4 associated with faster growth. In addition, using a genetic model of intestinal tumorigenesis where adenomatous polyposis coli (Apc) mutations lead to initiation of the tumorigenic process (Apcmin mice), we show that inactivation of a single allele of EphB4 results in higher proliferation in both the normal epithelium and intestinal tumors, significantly larger tumors in the small intestine, and a 10-fold increase in the number of tumors in the large intestine. This was associated with a 25% reduction in the lifespan of Apcmin mice (P &amp;lt; 0.0001). Gene expression analysis showed that EphB4 mutations result in a profound transcriptional reprogramming, affecting genes involved in cell proliferation, remodeling of the extracellular matrix, and cell attachment to the basement membrane among other functional groups of genes. Importantly, in agreement with the expression profiling experiments, using an in vitro assay, we show that loss of EPHB4 in colon cancer cells results in a significantly increased potential to invade through a complex extracellular matrix. Collectively, these results indicate that EphB4 has tumor suppressor activities and that regulation of cell proliferation, extracellular matrix remodeling, and invasive potential are important mechanisms of tumor suppression. [Cancer Res 2009;69(18):7430–8]
Detection of Impaired Homologous Recombination Repair in NSCLC Cells and Tissues
Authors: Moritz Birkelbach, Natalie Ferraiolo, Liliana Gheorghiu, Heike N. Pfäffle, Benedict Daly, Michael I. Ebright, Cheryl Spencer, Carl O'Hara, Johnathan R. Whetstine, Cyril H. Benes, Lecia V. Sequist, Lee Zou, Jochen Dahm-Daphi, Lisa A. Kachnic, Henning Willers
Journal: Journal of Thoracic Oncology (2013)
Erythropoietin Activates Mitochondrial Biogenesis and Couples Red Cell Mass to Mitochondrial Mass in the Heart
Authors: Martha S. Carraway, Hagir B. Suliman, W. Schuyler Jones, Chien-Wen Chen, Abdelwahid Babiker, Claude A. Piantadosi
Journal: Circulation Research (2010)

Erythropoietin (EPO) is often administered to cardiac patients with anemia, particularly from chronic kidney disease, and stimulation of erythropoiesis may stabilize left ventricular and renal function by recruiting protective effects beyond the correction of anemia.We examined the hypothesis that EPO receptor (EpoR) ligand-binding, which activates endothelial NO synthase (eNOS), regulates the prosurvival program of mitochondrial biogenesis in the heart.We investigated the effects of EPO on mitochondrial biogenesis over 14 days in healthy mice. Mice expressing a mitochondrial green fluorescent protein reporter construct demonstrated sharp increases in myocardial mitochondrial density after 3 days of EPO administration that peaked at 7 days and surpassed hepatic or renal effects and anteceded significant increases in blood hemoglobin content. Quantitatively, in wild-type mice, complex II activity, state 3 respiration, and mtDNA copy number increased significantly; also, resting energy expenditure and natural running speed improved, with no evidence of an increase in left ventricular mass index. Mechanistically, EPO activated cardiac mitochondrial biogenesis by enhancement of nuclear respiratory factor-1, PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha), and mitochondrial transcription factor-A gene expression in wild-type but not in eNOS(-/-) or protein kinase B (Akt1)(-/-) mice. EpoR was required, because EpoR silencing in cardiomyocytes blocked EPO-mediated nuclear translocation of nuclear respiratory factor-1.These findings support a new physiological and protective role for EPO, acting through its cell surface receptor and eNOS-Akt1 signal transduction, in matching cardiac mitochondrial mass to the convective O(2) transport capacity as erythrocyte mass expands.
Endothelial Protein Kinase C Isoform Identity and Differential Activity of PKCζ in an Athero-Susceptible Region of Porcine Aorta
Authors: Richard Magid, Peter F. Davies
Journal: Circulation Research (2005)

Endothelial protein kinase C (PKC) signaling was investigated in different regions of normal porcine aorta. The locations map to differential atherosclerotic susceptibility and correlate with sites of disturbed (DF) or undisturbed (UF) local flow profiles. Endothelial lysates were isolated from the inner curvature of the aortic arch (DF; athero-susceptible) and a nearby UF region of the descending thoracic aorta (UF; athero-protected), and in some experiments a distant athero-protected UF site, the common carotid artery. Total endothelial PKC activity in the DF regions was 145% to 240% of that in both UF locations ( P &lt;0.05), whereas the UF regions were not significantly different from each other. PKC protein isoforms α, β, ε, ι, λ, and ζ were expressed in similar proportions in both aortic regions, suggesting that differences of kinase activity were not directly attributable to expression levels. Inhibition of members of the “conventional” and “novel” PKC families had no differential effect on regional kinase activity. However, inhibition of PKCζ, a member of the “atypical” PKC family, reduced the DF lysate kinase activity to that of UF levels (NS P =0.35). Differential phosphorylation of PKCζ Thr410 and Thr560, along with increased levels of PKCζ degradation products in UF endothelial lysates, suggested posttranslational modification of PKCζ as the basis for site-specific differences in vivo. Steady-state regional heterogeneity of an important family of regulatory proteins in intact arterial endothelium in vivo may link localized athero-susceptibility and the associated hemodynamic environment.
Genetic mapping of ecotropic murine leukemia virus-inducing loci in six inbred strains.
Authors: C A Kozak, W P Rowe
Journal: The Journal of Experimental Medicine (1982)

Mendelian segregation analysis was used to map chromosomal genes for the induction of endogenous N- and B-tropic ecotropic retroviruses (V loci) in high and low leukemic mouse strains. Patterns of virus expression were determined for mice of various inbred strains, congenic lines carrying single V loci, and the linkage testing stocks used in mapping studies. Segregation analysis resulted in the genetic mapping of V loci from six inbred strains to five mouse chromosomes. The V locus of A/J was mapped to chromosome 5 and shown to be allelic with that of BALB/cJ and C3H/HeJ (Cv); this suggests that Cv-represents a stable ancestral V locus present in Bagg albino stocks before the separation of inbred lines. The single, poorly inducible V locus of C57BL/10J and one of the four high virus loci of C58/Lw were mapped to the same region of chromosome 8 and may represent an allelic pair with different patterns of expression. An N-tropic V locus of the SEA/GnJ mouse was mapped to chromosome 9, and one of the three V loci of C3H/FgLw was mapped to chromosome 7. The endogenous B-tropic virus of B10.BR/SgLi was mapped to chromosome 11. These studies provide further evidence that endogenous ecotropic V loci are present at different chromosomal sites in unrelated mouse strains and emphasize the role of germ line reinfections in the generation of this diversity.