tbuckley/cabot-search huggingface dataset:
Simultaneous Expression of Furin and Vascular Endothelial Growth Factor in Human Oral Tongue Squamous Cell Carcinoma Progression
Authors: Ricardo López de Cicco, James C. Watson, Daniel E. Bassi, Samuel Litwin, Andrés J. Klein-Szanto
Journal: Clinical Cancer Research (2004)

Squamous cell carcinoma (SCC) of the tongue is a common malignancy of the oral cavity. Furin convertase activates several precursor matrix metalloproteinases involved in the degradation of the extracellular matrix. The pattern of expression of furin and vascular endothelial growth factor-C (VEGF-C), two key molecules in neoplasm development, was examined during the progression from normal epithelium to invasive SCC.We evaluated furin and VEGF-C expression and microvessel density (MVD) by immunohistochemistry in human tongue sections harboring normal epithelium, dysplastic epithelium, and/or SCC. Sections from 46 glossectomy specimens were assessed for furin expression. A selected group of 15 cases, each containing normal epithelium, precursor lesions, and invasive SCC, were further studied for furin and VEGF-C expression and MVD quantification. We also evaluated the pattern of furin expression and VEGF-C processing by Western blot analysis in three SCC cell lines with different degrees of aggressiveness.Furin and VEGF-C expression was notably higher in most precursor lesions and SCCs than in normal epithelia. Approximately 60% (n = 26) and 100% (n = 15) of the normal epithelia showed low-intensity staining for furin and VEGF-C, respectively. Intense staining for furin and VEGF-C was detected in approximately 80% (n = 34) and 100% (n = 15) of the SCCs, respectively. A significant correlation was seen between the expression of these two markers (Spearman's test, P < 0.00002). We found a statistically significant increase in MVD when either dysplasia (432 +/- 19.06; P < 0.05) or SCC (546 +/- 17.24) was compared with normal epithelium (315 +/- 17.27; P < 0.0001). SCC71, the most aggressive cell line analyzed, was the one with the highest furin expression. This cell line totally processed the VEGF-C proform, whereas the less aggressive line SCC9, exhibiting the least furin expression, did not. SCC15, of intermediate aggressiveness and furin expression, showed intermediate pro-VEGF-C processing.These findings suggest that furin is a useful marker of tumor progression and is responsible for VEGF-C processing. This in turn would enhance angiogenesis, leading to increased MVD associated with preinvasive and invasive neoplasia.
Increased c-Jun-NH2-Kinase Signaling in Neurofibromatosis-1 Heterozygous Microglia Drives Microglia Activation and Promotes Optic Glioma Proliferation
Authors: Girish C. Daginakatte, Scott M. Gianino, Nina W. Zhao, Alexander S. Parsadanian, David H. Gutmann
Journal: Cancer Research (2008)

Abstract Neurofibromatosis-1 (NF1) is a common tumor predisposition syndrome in which affected individuals develop benign and malignant tumors. Previous studies from our laboratory and others have shown that benign tumor formation in Nf1 genetically engineered mice (GEM) requires a permissive tumor microenvironment. In the central nervous system, Nf1 loss in glia is insufficient for glioma formation unless coupled with Nf1 heterozygosity in the brain. Our subsequent studies identified Nf1+/− microglia as a critical cellular determinant of optic glioma growth in Nf1 GEM. Using NF1 as an experimental paradigm to further characterize the role of microglia in glioma growth, we first examined the properties of Nf1+/− microglia in vitro and in vivo. Nf1+/− microglia exhibit increased proliferation and motility and express elevated levels of genes associated with microglia activation. We further show that Nf1+/− microglia harbor high levels of activated c-Jun-NH2-kinase (JNK) without any significant changes in Akt, mitogen-activated protein kinase (MAPK), or p38-MAPK activity. In contrast, Nf1−/− astrocytes do not exhibit increased JNK activation. SP600125 inhibition of JNK activity in Nf1+/− microglia results in amelioration of the increased proliferation and motility phenotypes and reduces the levels of expression of activated microglia-associated transcripts. Moreover, SP600125 treatment of Nf1 optic glioma–bearing GEM results in reduced optic glioma proliferation in vivo. Collectively, these findings suggest that Nf1+/− microglia represent a good model system to study the role of specialized microglia in brain tumorigenesis and identify a unique Nf1 deregulated pathway for therapeutic studies aimed at abrogating microenvironmental signals that promote brain tumor growth. [Cancer Res 2008;68(24):10358–66]
Paraneoplastic limbic encephalitis and possible narcolepsy in a patient with testicular cancer: Case study
Authors: Joseph C. Landolfi, Mangala Nadkarni
Journal: Neuro-Oncology (2003)

We describe a patient who presented with a clinical syndrome of limbic encephalitis, narcolepsy, and cataplexy. The anti-Ma2 antibody was positive. Although there was no mass on imaging, orchiectomy was performed in this patient, and testicular carcinoma was found. This is the first known case of limbic encephalitis and anti-Ma2 antibody to be associated with cataplexy and possible narcolepsy. Neurological symptoms precede the diagnosis of cancer in 50% of patients with paraneoplastic syndromes, and clinicians are therefore strongly advised to evaluate patients with neurological symptoms for this condition.
Identification of a Proliferation Signature Related to Survival in Nodal Peripheral T-Cell Lymphomas
Authors: Marta Cuadros, Sandeep S. Dave, Elaine S. Jaffe, Emiliano Honrado, Roger Milne, Javier Alves, Jose Rodríguez, Magdalena Zajac, Javier Benitez, Louis M. Staudt, Beatriz Martinez-Delgado
Journal: Journal of Clinical Oncology (2007)

Nodal peripheral T-cell lymphomas (PTCLs) constitute a heterogeneous group of neoplasms, suggesting the existence of molecular differences contributing to their histologic and clinical variability. Initial expression profiling studies of T-cell lymphomas have been inconclusive in yielding clinically relevant insights. We applied DNA microarrays to gain insight into the molecular signatures associated with prognosis.We analyzed the expression profiles of 35 nodal PTCLs (23 PTCLs unspecified and 12 angioimmunoblastic) using two different microarray platforms, the cDNA microarray developed at the Spanish National Cancer Centre and an oligonucleotide microarray.We identified five clusters of genes, the expression of which varied significantly among the samples. Genes in these clusters seemed to be functionally related to different cellular processes such as proliferation, inflammatory response, and T-cell or B-cell lineages. Regardless of the microarray platform used, overexpression of genes in the proliferation signature was associated significantly with shorter survival of patients. This proliferation signature included genes commonly associated with the cell cycle, such as CCNA, CCNB, TOP2A, and PCNA. Moreover the PTCL proliferation signature showed a statistically significant inverse correlation with clusters of the inflammatory response (P < .0001), as well as with the percentage of CD68(+) cells.Our findings indicate that proliferation could be an important factor in evaluating nodal PTCL outcome and may help to define a more aggressive phenotype.
Toll-like receptor 9 (TLR9) is present in murine liver sinusoidal endothelial cells (LSECs) and mediates the effect of CpG-oligonucleotides
Authors: Montserrat Martin-Armas, Jaione Simon-Santamaria, Ingvild Pettersen, Ugo Moens, Bård Smedsrød, Baldur Sveinbjørnsson
Journal: Journal of Hepatology (2005)
Distinct contributions of TNF and LT cytokines to the development of dendritic cells in vitro and their recruitment in vivo
Authors: Koichiro Abe, Felix O. Yarovinsky, Takaya Murakami, Alexander N. Shakhov, Alexei V. Tumanov, Daisuke Ito, Ludmila N. Drutskaya, Klaus Pfeffer, Dmitry V. Kuprash, Kristin L. Komschlies, Sergei A. Nedospasov
Journal: Blood (2003)
Tetracycline-controlled transgenic targeting from the SCL locus directs conditional expression to erythrocytes, megakaryocytes, granulocytes, and c-kit-expressing lineage-negative hematopoietic cells
Authors: Ernesto Bockamp, Cecilia Antunes, Marko Maringer, Rosario Heck, Katrin Presser, Sven Beilke, Svetlana Ohngemach, Rudiger Alt, Michael Cross, Rolf Sprengel, Udo Hartwig, Bernd Kaina, Steffen Schmitt, Leonid Eshkind
Journal: Blood (2006)
Blood group isoantibody stimulation in man by feeding blood group-active bacteria
Authors: Georg F. Springer, Richard E. Horton
Journal: Journal of Clinical Investigation (1969)

It was investigated whether or not the human blood group isoantibodies A and B could be induced by immunogenic stimuli via natural routes with a kind of antigenic substance to which all humans are commonly exposed, or if the appearance of these antibodies is independent of antigenic stimuli as has long been believed. Escherichia coli O(86), which possess high human blood group B and faint A activity in vitro, were fed to healthy humans and those with intestinal disorders. 80% of the sick individuals of blood group O and A responded with a significant rise of anti-B antibodies which was frequently de novo in infants; significant increase of anti-A isoantibodies among blood group O individuals was less frequent. Over one-third of the healthy individuals also had a significant isoantibody increase. Intestinal lesions favor isoantibody stimulation by intestinal bacteria; this view was supported by the study of control infants. Persons of blood group A responded more frequently with anti-B and anti-E. coli O(86) antibody production than those of blood group O. Isoantibody increase was accompanied with antibody rise against E. coli O(86). Inhalation of E. coli O(86) or blood group AH(O)-specific hog mucin also evoked isoantibodies. The induced isoantibodies were specifically inhibited by small amounts of human blood group substances. E. coli O(86)-induced anti-blood group antibodies in germ-free chickens and preexisting blood group antibodies in ordinary chickens were neutralized by intravenous injection of E. coli O(86) lipopolysaccharide. This study demonstrates that human isoantibodies A and B are readily elicited via physiological routes, by blood group-active E. coli, provided the genetically determined apparatus of the host is responsive. Antibodies against a person's own blood group were not formed. Interpretation of these results permits some careful generalizations as to the origin of so-called natural antibodies.
Recurrent jaundice caused by recurrent hyperemesis gravidarum.
Authors: D Larrey, B Rueff, G Feldmann, C Degott, G Danan, J P Benhamou
Journal: Gut (1984)

The existence of jaundice induced by hyperemesis gravidarum is controversial. We report the case of a woman who suffered from three episodes of jaundice during the first trimester of three consecutive pregnancies, a few days after the onset of hyperemesis gravidarum. Jaundice was caused by conjugated hyperbilirubinaemia. Serum alanine aminotransferase activity was increased and scarce necrotic hepatocytes were shown on light and electron microscopic examinations. Cessation of vomiting was rapidly followed by complete recovery. This observation supports the view that severe vomiting can cause jaundice in pregnant women.
Mesenchymal cystic hamartoma? A revised diagnosis after 23 years
Authors: Erik H F M van der Heijden, Suzanne E J Kaal, Henk H M Hassing, Ad F T M Verhagen, Monica Looijen-Salamon
Journal: Thorax (2013)

In 1994, we published a rare case report of a left sided pneumothorax caused by a mesenchymal cystic hamartoma (MCH) in this journal ( Thorax 1994;49:1175–6).1 

After a follow-up of 23 years, the same patient was referred for a left sided pain and thoracic mass at age 36 years. At age 14 years, a left sided thoracotomy was performed for recurrent pneumothorax followed by lobectomy of the left lower lobe in which a MCH was diagnosed.1 Now his symptoms started almost 1 year before referral. Analysis showed an inhomogeneous mass in the lower left thoracic cavity with metabolic activity on the F-18-fluorodeoxyglucose positron emission tomography-PET scan. Follow up CT-scans showed slow progression (figure 1) and CT-guided biopsy showed a monophasic malignant tumour consisting of spindle cells, immunohistochemically positive for vimentin and epithelial membrane antigen (EMA) …
Optimizing Radiolabeled Engineered Anti-p185HER2 Antibody Fragments for<i>In vivo</i>Imaging
Authors: Tove Olafsen, Vania E. Kenanova, Gobalakrishnan Sundaresan, Anne-Line Anderson, Desiree Crow, Paul J. Yazaki, Lin Li, Michael F. Press, Sanjiv S. Gambhir, Lawrence E. Williams, Jeffrey Y.C. Wong, Andrew A. Raubitschek, John E. Shively, Anna M. Wu
Journal: Cancer Research (2005)

Abstract We have recently described the in vivo properties of an iodinated anti-p185HER2 engineered antibody fragment [minibody (scFv-CH3)2; 80 kDa], made from the internalizing 10H8 monoclonal antibody. Although the 10H8 minibody showed excellent binding to the target in vitro, only modest tumor uptake [5.6 ± 1.7% injected dose per gram (ID/g) of tissue] was achieved in nude mice bearing MCF7/HER2 breast cancer tumors. Here, in an attempt to improve targeting, the 10H8 minibody was conjugated to 1,4,7,10-tetraazacyclododecane-N, N′, N′′, N′′′-tetraacetic acid (DOTA), radiometal labeled, and evaluated in vivo. The tumor uptake of 111In-DOTA 10H8 minibody was 5.7 ± 0.1% ID/g, similar to the radioiodinated 10H8 minibody. However, in addition to the expected liver clearance, the kidneys had unexpectedly high activity (34.0 ± 4.0% ID/g). A minibody derived from a second anti-p185HER2 antibody (trastuzumab; hu4D5v8) was also made. Tumor uptakes, evaluated by quantitative microPET using 64Cu-DOTA hu4D5v8 minibody, were 4.2 ± 0.5% ID/g. Furthermore, in non-tumor-bearing mice, 111In-DOTA hu4D5v8 minibody exhibited similar elevated uptake in the kidneys (28.4 ± 6.5% ID/g). Immunohistochemical staining of kidneys from non-tumor-bearing mice showed strong specific staining of the proximal tubules, and Western blot analysis of kidney lysate confirmed the presence of cross-reactive antigen. To further improve tumor uptake and normal tissue distribution, a larger hu4D5v8 fragment [(scFv-CH2-CH3)2; 105 kDa] was made, engineered to exhibit rapid clearance kinetics. This fragment, when evaluated by microPET, exhibited improved tumor targeting (12.2 ± 2.4% ID/g) and reduced kidney uptake (13.1 ± 1.5% ID/g). Thus, by manipulating the size and format of anti-p185HER2 antibody fragments, the kidney activity was reduced and high or low expression of p185HER2 in xenografts could be distinguished by microPET imaging.
Avidity maturation of memory CD8 T cells is limited by self-antigen expression
Authors: Michael J. Turner, Evan R. Jellison, Elizabeth G. Lingenheld, Lynn Puddington, Leo Lefrançois
Journal: The Journal of Experimental Medicine (2008)

Immune tolerance to self-antigens is a complex process that utilizes multiple mechanisms working in concert to maintain homeostasis and prevent autoimmunity. We developed a system that revealed a population of self-specific CD8 T cells within the endogenous T cell repertoire. Immunization of ovalbumin (OVA)-expressing transgenic mice with recombinant viruses expressing OVA-peptide variants induced self-reactive T cells in vivo that matured into memory T cells able to respond to secondary infection. However, whereas the avidity of memory cells in normal mice increased dramatically with repeated immunizations, avidity maturation was limited for self-specific CD8 T cells. Despite decreased avidity, such memory cells afforded protection against infection, but did not induce overt autoimmunity. Further, up-regulation of self-antigen expression in dendritic cells using an inducible system promoted programmed death-1 expression, but not clonal expansion of preexisting memory cells. Thus, the self-reactive T cell repertoire is controlled by overlapping mechanisms influenced by antigen dose.
The Folate Receptor α Is Frequently Overexpressed in Osteosarcoma Samples and Plays a Role in the Uptake of the Physiologic Substrate 5-Methyltetrahydrofolate
Authors: Rui Yang, E. Anders Kolb, Jing Qin, Alexander Chou, Rebecca Sowers, Bang Hoang, John H. Healey, Andrew G. Huvos, Paul A. Meyers, Richard Gorlick
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Two major systems exist for folate cell entry: the reduced folate carrier (RFC) and the folate receptor (FR). Although defective RFC-mediated transport was frequently identified as a mechanism of methotrexate (MTX) resistance in osteosarcoma, the status of FR and its role in this disease are unknown. Experimental Design: mRNA for FRα was measured in 107 osteosarcoma specimens using quantitative reverse transcription-PCR and was related to RFC expression. The effect of FRα overexpression on MTX resistance and natural folate uptake was studied using FRα non-expressing osteosarcoma 143B cells transfected with FRα cDNA in comparison with those transfected with sense or antisense RFC in the same genetic background. Results: Eighty-four samples (78.5%) had detectable FRα mRNA, and 29.9% had higher levels than the ovarian cancer cell line SKOV-3. No correlation was found between mRNA levels of FRα and RFC (r2 = 0.002). FRα overexpression had minor effects on the transport of MTX and sensitivity to this drug. Among the transfected 143B sublines, only the 143B-FRα was able to uptake 5-methyltetrahydrofolate when the extracellular concentration was reduced to 2 nmol/L, which conferred a growth advantage in physiologic folate concentrations compared with vector-only–transfected cells. Importantly, this was not similarly achieved by RFC overexpression. Conclusions: This study suggests that FRα plays a role in the uptake of 5-methyltetrahydrofolate when the concentration gradient is insufficient for RFC-mediated transport. FRα overexpression is unlikely secondary to the decreased RFC expression in osteosarcoma.
Long-Term Outcome of Lithium Prophylaxis in Bipolar Disorder: A 5-Year Prospective Study of 402 Patients at a Lithium Clinic
Authors: M Maj, R Pirozzi, L Magliano, L Bartoli
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: In this prospective study, information was collected on all bipolar I patients who started lithium prophylaxis at a lithium clinic during more than 15 years. METHOD: Patients were evaluated bimonthly with standardized instruments for as long as they took lithium. Treatment surveillance conformed to internationally accepted guidelines. Five years after starting prophylaxis, each patient was contacted for a follow-up interview. RESULTS: Of the 402 enrolled patients, 27.9% were no longer taking lithium at follow-up; 38.1% were taking lithium and had had at least one recurrence of the disorder; and 23.4% were taking lithium and had had no recurrence. Among patients still taking lithium whose plasma lithium levels had been below 0.5 mmol/liter on no more than 10% of checks, 88.0% had at least a 50% reduction in mean annual time spent in the hospital compared to a reference pretreatment period, and 43.0% had had no recurrence. Patients not taking lithium at follow-up had a poorer outcome than those taking lithium, but patients no longer taking any psychotropic drug did not differ from those taking lithium. Patients no longer taking lithium had had a higher frequency of psychotic features in the index episode than those still taking lithium. CONCLUSIONS: The impact of lithium prophylaxis on the course of bipolar disorder is severely limited by the high dropout rate. In bipolar patients taking lithium regularly for several years, a drastic reduction of time spent in the hospital is almost the rule; these patients represent a self-selected population in which at least one group at high risk of poor outcome is underrepresented. (Am J Psychiatry 1998; 155:30–35)
Genetic and Environmental Determinants of Human NK Cell Diversity Revealed by Mass Cytometry
Authors: Amir Horowitz, Dara M. Strauss-Albee, Michael Leipold, Jessica Kubo, Neda Nemat-Gorgani, Ozge C. Dogan, Cornelia L. Dekker, Sally Mackey, Holden Maecker, Gary E. Swan, Mark M. Davis, Paul J. Norman, Lisbeth A. Guethlein, Manisha Desai, Peter Parham, Catherine A. Blish
Journal: Science Translational Medicine (2013)

Both genetics and environment contribute to human NK cell diversity.
P5 Airway responsiveness measurements in asthmatic recruits to emergency services
Authors: S. Wiscombe, V. Jeebun, S. Stenton
Journal: Thorax (2010)

<h3></h3> Asthmatics undertaking emergency service work are thought to be at increased risk of severe bronchoconstriction with sudden exertion or exposure to irritants such as fire smoke, pepper spray or CS gas. The risks are poorly quantified and there are no clear guidelines to assist employers. We investigated the value of airway responsiveness measurements in 40 applicants to the police service who were thought to have asthma at a pre-employment examination. Their mean age was 25 years (SD 6 years); 22 (55%) were male. Only 15 (37%) reported active symptoms (wheeze, breathlessness or cough). Their median FEV1 was 106% of predicted (range 77–125%) and only 3 demonstrated airflow obstruction. Airway responsiveness was measured as PD<sub>20</sub>.FEV<sub>1</sub> to methacholine using the Newcastle dosimeter technique1 16 (40%) had measurements in the ‘definite’ asthma range, that is, PD<sub>20</sub>.FEV<sub>1</sub>&lt;200 μg; 6 in the “equivocal” range PD<sub>20</sub>.FEV<sub>1</sub>&lt;200–1000 μg; and 18 in the ‘normal’ range PD<sub>20</sub>.FEV<sub>1</sub>&gt;1000 μg. There was a clear relationship between pre-employment FEV1 and PD20 within the definite asthma group (F<sub>(1,14)</sub>= 9.15; p&lt;0.001) but there were no significant associations between PD20 category and symptoms, medication use or lung function. We conclude that airway responsiveness measurements are practical in this setting and identify more than 50% of asthmatics as probably at low risk of marked bronchoconstriction. Further follow-up of the cohort will be necessary to more precisely determine the risks (Abstract P5 Table 1).
Prevalence of spondyloarthritis in reference to HLA-B27 in the French population: results of the GAZEL cohort
Authors: Félicie Costantino, Alice Talpin, Roula Said-Nahal, Marcel Goldberg, Joseph Henny, Gilles Chiocchia, Henri-Jean Garchon, Marie Zins, Maxime Breban
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To estimate the prevalence of spondyloarthritis (SpA) in reference to HLA-B27 in the French population. <h3>Methods</h3> In 1989, 20 625 employees of the French national gas and electricity company aged 35–50 years were enrolled in the GAZEL cohort. In 2010, 18 757 still active participants were screened by a questionnaire validated for the detection of SpA. Responders with available DNA were retained for further studies. Pelvic radiograph and HLA-B27 typing were performed in all the self-reported cases of SpA or psoriatic arthritis. Self-reported diagnosis was verified by a qualified rheumatologist. HLA-B27 determination was also performed in subjects without any SpA feature. <h3>Results</h3> The target population consisted of 6556 responders with available DNA. Their male:female ratio was 3.6 and their mean age was 65.5±3.3 years. A diagnosis of SpA was confirmed in 32 of the 72 self-reported cases, 75% of them being HLA-B27 positive. Estimated SpA prevalence adjusted for sex was 0.43% (95% CI 0.26% to 0.70%). HLA-B27 positivity rate in 2466 healthy controls was 6.9% (95% CI 5.9% to 7.9%). The relative risk of SpA in HLA-B27 positive individuals was 39 (95% CI 17 to 86). <h3>Conclusions</h3> We estimated the prevalence of SpA in the French population in 2010 to 0.43%. With an estimated prevalence of 75.0% in SpA and 6.9% in healthy controls, HLA-B27 increased the disease risk 39-fold, as compared with HLA-B27 negative subjects.