tbuckley/cabot-search huggingface dataset:
cDNA cloning of the B cell membrane protein CD22: a mediator of B-B cell interactions.
Authors: G L Wilson, C H Fox, A S Fauci, J H Kehrl
Journal: The Journal of Experimental Medicine (1991)

We have cloned a full-length cDNA for the B cell membrane protein CD22, which is referred to as B lymphocyte cell adhesion molecule (BL-CAM). Using subtractive hybridization techniques, several B lymphocyte-specific cDNAs were isolated. Northern blot analysis with one of the clones, clone 66, revealed expression in normal activated B cells and a variety of B cell lines, but not in normal activated T cells, T cell lines, Hela cells, or several tissues, including brain and placenta. One major transcript of approximately 3.3 kb was found in B cells although several smaller transcripts were also present in low amounts (approximately 2.6, 2.3, and 1.6 kb). Sequence analysis of a full-length cDNA clone revealed an open reading frame of 2,541 bases coding for a predicted protein of 847 amino acids with a molecular mass of 95 kD. The BL-CAM cDNA is nearly identical to a recently isolated cDNA clone for CD22, with the exception of an additional 531 bases in the coding region of BL-CAM. BL-CAM has a predicted transmembrane spanning region and a 140-amino acid intracytoplasmic domain. Search of the National Biological Research Foundation protein database revealed that this protein is a member of the immunoglobulin super family and that it had significant homology with three homotypic cell adhesion proteins: carcinoembryonic antigen (29% identity over 460 amino acids), myelin-associated glycoprotein (27% identity over 425 amino acids), and neural cell adhesion molecule (21.5% over 274 amino acids). Northern blot analysis revealed low-level BL-CAM mRNA expression in unactivated tonsillar B cells, which was rapidly increased after B cell activation with Staphylococcus aureus Cowan strain 1 and phorbol myristate acetate, but not by various cytokines, including interleukin 4 (IL-4), IL-6, and gamma interferon. In situ hybridization with an antisense BL-CAM RNA probe revealed expression in B cell-rich areas in tonsil and lymph node, although the most striking hybridization was in the germinal centers. COS cells transfected with a BL-CAM expression vector were immunofluorescently stained positively with two different CD22 antibodies, each of which recognizes a different epitope. Additionally, both normal tonsil B cells and a B cell line were found to adhere to COS transfected with BL-CAM in the sense but not the antisense direction.(ABSTRACT TRUNCATED AT 400 WORDS)
A Novel Engineered Anti-CD20 Tracer Enables Early Time PET Imaging in a Humanized Transgenic Mouse Model of B-cell Non-Hodgkins Lymphoma
Authors: Arutselvan Natarajan, Benjamin J. Hackel, Sanjiv Sam Gambhir
Journal: Clinical Cancer Research (2013)

The aim of this article was to evaluate the use of a novel engineered anti-CD20 protein based on the 10 kDa human fibronectin type 3 domain (FN3) and subsequently compare with (64)Cu-rituximab for positron emission tomography (PET) imaging of CD20.The engineered FN3(CD20) and FN3(WT) were produced in Escherichia coli cells at 2 to 5 mg/L, conjugated to DOTA, labeled with (64)Cu, and used for PET imaging of huCD20 expression in B cells. Humanized transgenic mice and subcutaneously xenografted mice each received intravenous (64)Cu-FN3(CD20) or FN3(WT) (3.7 MBq/4 μg Do-FN3 in 200 μL PBS). Control group received a blocking dose (50-fold excess) of unconjugated FN3(CD20) two hours before radiotracer injection. PET imaging was carried out at 1 to 24 hours postinjections.In vitro assay demonstrated FN3 binds CD20 with 20 nmol/L affinity on CD20-expressing cells. (64)Cu-FN3(CD20) showed clear, high-contrast visualization of huCD20-expressing B cells in the spleen of transgenic mice as early as 1 hour postinjection [38 ± 3% injected dose (ID)/g] and exhibited a spleen-to-blood ratio of 13 by 4 hours. This is higher uptake (P = 0.04) and 10-fold greater signal-to-background (P = 0.04) than the (64)Cu-rituximab antibody radiotracer. Tumor uptake (16.8 ± 1.6 vs. 5.6 ± 1.4%ID/g) and tumor:background ratios were superior for FN3CD20 relative to rituximab in xenograft studies as well.The (64)Cu-Do-FN3(CD20) radiotracer represents a novel small, high-affinity binder for imaging human CD20, which may be well suited for B-cell non-Hodgkin's lymphoma imaging in patients at early time points.
Efficacy of a quadrivalent prophylactic human papillomavirus (types 6, 11, 16, and 18) L1 virus-like-particle vaccine against high-grade vulval and vaginal lesions: a combined analysis of three randomised clinical trials
Authors: Elmar A Joura, Sepp Leodolter, Mauricio Hernandez-Avila, Cosette M Wheeler, Gonzalo Perez, Laura A Koutsky, Suzanne M Garland, Diane M Harper, Grace WK Tang, Daron G Ferris, Marc Steben, Ronald W Jones, Janine Bryan, Frank J Taddeo, Oliver M Bautista, Mark T Esser, Heather L Sings, Micki Nelson, John W Boslego, Carlos Sattler, Eliav Barr, Jorma Paavonen
Journal: The Lancet (2007)
Effect of centre on outcome of bone-marrow transplantation for acute myeloid leukaemia
Authors: Francesco Frassoni, Myriam Labopin, Ray Powles, Jean-Yves Mary, William Arcese, Andrea Bacigalupo, Donald Bunjes, Eliane Gluckman, Tapani Ruutu, Ulrich W Schaefer, Jorge Sierra, Jean Paul Vernant, Roel Willemze, Theo de Witte, Norbert Claude Gorin Transplantation
Journal: The Lancet (2000)
Prevalence of <i>bcl-2</i> Rearrangement in Patients with Hepatitis C Virus–Related Mixed Cryoglobulinemia with or without B-Cell Lymphomas
Authors: Anna Linda Zignego, Clodoveo Ferri, Francesca Giannelli, Carlo Giannini, Patrizio Caini, Monica Monti, Maria Eugenia Marrocchi, Elena Di Pietro, Giorgio La Villa, Giacomo Laffi, Paolo Gentilini
Journal: Annals of Internal Medicine (2002)

Background: Hepatitis C virus (HCV) infection is strictly associated with mixed cryoglobulinemia, a benign B-cell lymphoproliferative disorder that may evolve to lymphoma. An increased prevalence of bcl-2 rearrangement (the t[14; 18] translocation) has been shown in patients infected with HCV. Objective: To evaluate the prevalence of bcl-2 rearrangement in patients with HCV-related mixed cryoglobulinemia and patients with chronic hepatitis but no cryoglobulinemia. Design: Prospective study. Setting: Two university hospitals. Patients: 37 consecutively recruited patients with HCV-related mixed cryoglobulinemia and 101 patients with chronic HCV infection but without mixed cryoglobulinemia. Measurements: Clinical and serologic characteristics; liver biopsy; bcl-2 rearrangement, Bcl-2 expression, and the ratio of Bcl-2 to Bax in total peripheral blood mononuclear cells and cell subgroups; and sequence analysis of the junction of bcl-2 and IgH joining segments in positive samples. Results: Rearrangement of bcl-2 was observed in 28 of 37 (75.7%) patients with mixed cryoglobulinemia (65% of those with type III disease and 85% of those with type II disease, including 3 of 4 patients with lymphoma) and in 38 of 101 (37.6%) patients with chronic HCV infection but not mixed cryoglobulinemia (P < 0.001). Overexpression of Bcl-2 protein and a high ratio of Bcl-2 to Bax were observed in samples from patients with bcl-2 rearrangement. In 2 patients followed over time, peripheral blood cells bearing the t(14;18) translocation disappeared after antiviral therapy. Conclusions: Rearrangement of bcl-2 was found with increased frequency in patients with chronic HCV infection and mixed cryoglobulinemia. The frequency was greatest in patients with type II mixed cryoglobulinemia. The high ratio of Bcl-2 to Bax in patients with bcl-2 rearrangement and disappearance of the rearrangement with antiviral therapy suggest that the translocation is associated with the antiapoptotic function of Bcl-2 and that HCV infection is linked to inhibition of B-cell apoptosis.
Towards individualised treatment in COPD
Authors: J. Fingleton, M. Weatherall, R. Beasley
Journal: Thorax (2011)

The heterogeneous nature of chronic obstructive pulmonary disease (COPD) was recognised long before the term was popularised by Briscoe and Nash,1 and the original classifications of chronic bronchitis and emphysema remain more recognisable to the general public than the term COPD. The challenge in recent years has been to better characterise the different phenotypes that make up the syndrome of COPD and so develop a new classification and terminology for COPD. This is not an esoteric pursuit but a worthwhile endeavour which has the potential to shed light on the underlying pathophysiology, risk factors, natural history and treatment responses of the specific phenotypes. Ultimately, this has the potential to enable tailoring of treatment regimes to individual patients. Currently this is not possible as the treatment guidelines for COPD do not differ according to phenotype, other than by severity. Furthermore, the randomised controlled trials on which the guidelines are based study highly selected COPD subgroups, for which only a minority of people with COPD would have been eligible for inclusion.2 As a result, the findings have limited external validity and are poorly generalisable to patients with COPD managed in the community. This means not only that is there an inadequate evidence base for the majority of patients with COPD, but also that treatments which may provide benefit only to certain phenotypes are unlikely to be identified.

A variety of methods have been used to explore the different phenotypes of COPD. Early studies constructed groups based on recognised clinical patterns, informed by those variables which were significantly associated with outcome. For example, in 1987 Burrows et al 3 described three groups of patients with chronic airways obstruction, one considered to have features most characteristic of chronic asthma, a second comprising non-atopic smokers without known asthma and an intermediate third group. …
Expression of HIV transgene aggravates kidney injury in diabetic mice
Authors: Sandeep K. Mallipattu, Ruijie Liu, Yifei Zhong, Ed Y. Chen, Vivette D'Agati, Lewis Kaufman, Avi Ma'ayan, Paul E. Klotman, Peter Y. Chuang, John C. He
Journal: Kidney International (2013)

With the widespread use of combination antiretroviral agents, the incidence of HIV-associated nephropathy has decreased. Currently, HIV-infected patients live much longer and often suffer from comorbidities such as diabetes mellitus. Recent epidemiological studies suggest that concurrent HIV infection and diabetes mellitus may have a synergistic effect on the incidence of chronic kidney disease. To address this, we determined whether HIV-1 transgene expression accelerates diabetic kidney injury using a diabetic HIV-1 transgenic (Tg26) murine model. Diabetes was initially induced with low-dose streptozotocin in both Tg26 and wild-type mice on a C57BL/6 background, which is resistant to classic HIV-associated nephropathy. Although diabetic nephropathy is minimally observed on the C57BL/6 background, diabetic Tg26 mice exhibited a significant increase in glomerular injury compared with nondiabetic Tg26 mice and diabetic wild-type mice. Validation of microarray gene expression analysis from isolated glomeruli showed a significant upregulation of proinflammatory pathways in diabetic Tg26 mice. Thus, our study found that expression of HIV-1 genes aggravates diabetic kidney disease.
Clinical Observations on the Use of Digitalis in Heart Disease and Dropsy with Fibrillation of the Auricles (Nodal Rhythm)
Authors: J. D. Windle
Journal: BMJ (1911)

L[z BDLORNA 423 'bruit at the impulse; at the same time the heart is clearly " physiological " albuminuria, which needs no treatment *nd is not indicative of any underl3ing di£ease.ettInicaIr O1bsQerationrn
An old disease from a new perspective - GOLD 2011 recommendations for COPD
Authors: Renata Rubinsztajn, Tadeusz Przybylowski, Marta Maskey-Warzechowska, Krzysztof Karwat, Ryszarda Chazan
Journal: European Respiratory Journal (2012)

The GOLD 2011 recommendations for chronic obstructive pulmonary disease (COPD) introduce a new classification system to optimize treatment in individual patients. Except for FEV 1 , this classification incorporates dyspnea severity or the CAT score and the number of exacerbations.  The aim of our study was to compare the GOLD 2010 and 2011 COPD classification.  The study group consisted of 128 patients. Based on the post-bronchodilator FEV 1  only, as recommended in the GOLD 2010 report, there were 21 patients in stage I, 53 patients in II, 35 in III and 19 in IV, respectively. In all patients, the number of exacerbations per year was noted and dyspnea was assessed with the modified MRC scale. The patients were subsequently graded to group A,B,C, D as proposed in the combined COPD assessment in GOLD 2011.  We had problems with grading of 37 (28.9%) patients according to the GOLD 2011 criteria; there were 14 patients in GOLD stage I/II with≥ 2 exacerbations per year and 23 patients in GOLD stage III/IV with   We conclude that despite the fact that the new GOLD 2011 combined assessment is aimed at optimizing therapy, in clinical practice, there may be problems with patient classification. This especially concerns patients with mild/moderate airflow limitation and frequent exacerbations and those with severe airway obstruction without frequent exacerbations.
The Renin-Angiotensin System and Aldosterone Secretion during Sodium Depletion in the Rat
Authors: WILLIAM S. SPIELMAN, JAMES O. DAVIS
Journal: Circulation Research (1974)

The role of the renin-angiotensin system in the control of aldosterone secretion was studied in the sodium-depleted rat. Administration of angiotensin II produced a significant increase in aldosterone secretion and arterial blood pressure in normal rats; simultaneous infusion of the angiotensin analogue. 1-sarcosine-8-alanine-angiotensin II, blocked both the pressor and the steroidogenic actions of angiotensin. Since the angiotensin II analogue was effective in blocking exogenous angiotensin II, an attempt was made to block endogenously formed angiotensin II in the sodium-depleted rat; infusions of large doses of the analogue produced a significant fall in arterial blood pressure, but aldosterone secretion failed to change. Bilateral nephrectomy also failed to decrease aldosterone secretion in the sodium-depleted rat even though arterial blood pressure fell. Since the secretion of corticosterone in these rats was high, it seemed likely that the failure of aldosterone secretion to fall resulted from an overriding influence of adrenocorticotropic hormone (ACTH). To test this hypothesis, the renin-angiotensin system was again blocked in sodium-depleted rats with three levels of anterior pituitary function. With high or intermediate rates of corticosterone secretion, a nonapeptide converting enzyme inhibitor (CEI) failed to influence aldosterone secretion. However, when the influence of ACTH was completely eliminated by hypophysectomy in sodium-depleted rats, the nonapeptide CEI produced a striking fall in aldosterone secretion. In contrast, arterial blood pressure was significantly reduced by CEI in rats with all three levels of anterior pituitary function. The data suggest a role for angiotensin II in the regulation of aldosterone secretion and the maintenance of arterial blood pressure in the sodium-depleted rat.
A Diffusion Tensor Imaging Study of Fasciculi in Schizophrenia
Authors: Sukhwinder Shergill
Journal: American Journal of Psychiatry (2007)

Cognitive models propose that the symptoms and psychological impairments associated with schizophrenia arise as a consequence of impaired communication between brain regions, especially the prefrontal cortex and the temporal and parietal lobes. Functional imaging and electrophysiological data have provided evidence of functional dysconnectivity, but it is unclear whether this reflects an underlying problem with anatomical connectivity. This study used diffusion tensor imaging to examine the integrity of the major white matter fasciculi, which connects the frontal and temporal-parietal cortices, and the corpus callosum in patients with schizophrenia.A 1.5-T magnetic resonance scanner was used to acquire diffusion tensor images giving whole brain coverage at an isotropic 2.5-mm voxel size. Fractional anisotropy was measured in 33 patients with schizophrenia and 40 healthy comparison subjects with an automated voxel-based method of analysis.There was reduced fractional anisotropy in patients with schizophrenia in regions corresponding to the superior longitudinal fasciculi bilaterally and in the genu of the corpus callosum. However, within the patient group, the propensity to experience auditory hallucinations was associated with relatively increased fractional anisotropy in superior longitudinal fasciculi and in the anterior cingulum.Schizophrenia is associated with altered white matter integrity in the tracts connecting the frontal cortex with the temporal and parietal cortices and with the contralateral frontal and temporal lobes. The severity of these changes may vary with the pattern of symptoms associated with the disorder.
Vitamin D and skeletal muscle strength and endurance in COPD
Authors: Abigail S. Jackson, Dinesh Shrikrishna, Julia L. Kelly, Nicholas Hart, John Moxham, Michael I. Polkey, Paul Kemp, Nicholas S. Hopkinson
Journal: European Respiratory Journal (2012)

It is not known whether vitamin D levels make a significant contribution to muscle dysfunction in chronic obstructive pulmonary disease (COPD). In 104 COPD patients (mean± sd forced expiratory volume in 1 s 44±22 % predicted) and 100 age- and sex-matched controls, serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH) 2 D) and parathyroid hormone (PTH) levels were measured and related to quadriceps strength and endurance. In a subset of 26 patients and 13 controls, quadriceps biopsy was performed and mRNA expression of myogenic regulatory factors (mrf) and fibre-specific myosin heavy chains (MHC) was determined. COPD patients were weaker and less physically active than controls. 25(OH)D levels were similar in both groups (48.5±25.5 nmol·L −1 COPD versus 55.4±28.3 nmol·L −1 control, p=0.07) but PTH levels were significantly higher in patients (5.2±2.3 pmol·mL −1 versus 4.4±2.0 pmol·L −1 , p=0.01). 1,25(OH)D was significantly correlated with strength in controls, but not in COPD patients and not with quadriceps endurance assessed using repetitive magnetic stimulation in COPD (n=35) or control (n=35) subjects. In controls, but not COPD patients, muscle biopsy analysis showed a negative relationship between 25(OH)D and MHCIIa expression (r 2 =0.5, p=0.01) and a positive relationship between mrf4 and MHCIIa expression (r 2 =0.5, p=0.009), and myogenic regulatory factor myf5 and MHCI expression (r 2 =0.72, p=0.004). In contrast with healthy controls, muscle strength is not associated with vitamin D levels in COPD, which may represent vitamin D resistance.
Clinical Prediction Rule for Identifying Children With Cerebrospinal Fluid Pleocytosis at Very Low Risk of Bacterial Meningitis
Authors: Lise E. Nigrovic, Nathan Kuppermann, Charles G. Macias, Christopher R. Cannavino, Donna M. Moro-Sutherland, Robert D. Schremmer, Sandra H. Schwab, Dewesh Agrawal, Karim M. Mansour, Jonathan E. Bennett, Yiannis L. Katsogridakis, Michael M. Mohseni, Blake Bulloch, Dale W. Steele, Ron L. Kaplan, Martin I. Herman, Subhankar Bandyopadhyay, Peter Dayan, Uyen T. Truong, Vincent J. Wang, Bema K. Bonsu, Jennifer L. Chapman, John T. Kanegaye, Richard Malley
Journal: JAMA (2007)

Children with cerebrospinal fluid (CSF) pleocytosis are routinely admitted to the hospital and treated with parenteral antibiotics, although few have bacterial meningitis. We previously developed a clinical prediction rule, the Bacterial Meningitis Score, that classifies patients at very low risk of bacterial meningitis if they lack all of the following criteria: positive CSF Gram stain, CSF absolute neutrophil count (ANC) of at least 1000 cells/microL, CSF protein of at least 80 mg/dL, peripheral blood ANC of at least 10,000 cells/microL, and a history of seizure before or at the time of presentation.To validate the Bacterial Meningitis Score in the era of widespread pneumococcal conjugate vaccination.A multicenter, retrospective cohort study conducted in emergency departments of 20 US academic medical centers through the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. All children aged 29 days to 19 years who presented at participating emergency departments between January 1, 2001, and June 30, 2004, with CSF pleocytosis (CSF white blood cells > or =10 cells/microL) and who had not received antibiotic treatment before lumbar puncture.The sensitivity and negative predictive value of the Bacterial Meningitis Score.Among 3295 patients with CSF pleocytosis, 121 (3.7%; 95% confidence interval [CI], 3.1%-4.4%) had bacterial meningitis and 3174 (96.3%; 95% CI, 95.5%-96.9%) had aseptic meningitis. Of the 1714 patients categorized as very low risk for bacterial meningitis by the Bacterial Meningitis Score, only 2 had bacterial meningitis (sensitivity, 98.3%; 95% CI, 94.2%-99.8%; negative predictive value, 99.9%; 95% CI, 99.6%-100%), and both were younger than 2 months old. A total of 2518 patients (80%) with aseptic meningitis were hospitalized.This large multicenter study validates the Bacterial Meningitis Score prediction rule in the era of conjugate pneumococcal vaccine as an accurate decision support tool. The risk of bacterial meningitis is very low (0.1%) in patients with none of the criteria. The Bacterial Meningitis Score may be helpful to guide clinical decision making for the management of children presenting to emergency departments with CSF pleocytosis.
Combined modality treatment with a weekly brief chemotherapy (ACOP-B) followed by locoregional radiotherapy in localized-stage intermediate- to high-grade non-Hodgkin's lymphoma
Authors: R. Freilone, B. Botto, U. Vitolo, M. Bertini, E. Audisio, R. Calvi, M. Cucchi, A. De Crescenzo, A. Gallamini, R. Ghio, L. Griso, A. Levis, G. Massara, L. Orsucci, U. Ricardi, D. Rota Scalabrini, F. Salvi, V. Secondo, L. Resegotti
Journal: Annals of Oncology (1996)
TRANSFORMING GROWTH FACTOR-β REGULATION OF IMMUNE RESPONSES
Authors: Ming O. Li, Yisong Y. Wan, Shomyseh Sanjabi, Anna-Karin L. Robertson, Richard A. Flavell
Journal: Annual Review of Immunology (2005)

Transforming growth factor-β (TGF-β) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-β in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. In addition, TGF-β controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of lymphocytes, natural killer cells, dendritic cells, macrophages, mast cells, and granulocytes. The regulatory activity of TGF-β is modulated by the cell differentiation state and by the presence of inflammatory cytokines and costimulatory molecules. Collectively, TGF-β inhibits the development of immunopathology to self or nonharmful antigens without compromising immune responses to pathogens. This review highlights the findings that have advanced our understanding of TGF-β in the immune system and in disease.