tbuckley/cabot-search huggingface dataset:
LOCALIZATION OF ANTIBODIES IN GROUP I AND GROUP II γ-GLOBULINS
Authors: Mart Mannik, Henry G. Kunkel
Journal: The Journal of Experimental Medicine (1963)

A wide assortment of antibodies has been analysed by qualitative and quantitative techniques for their content of group I- and group II-type γ-globulin molecules. These included Rh antibodies, isoagglutinins, thyroglobulin antibodies, dextran antibodies, and teichoic acid antibodies. All the antibodies studied showed the presence of both groups. However, the ratio of the two varied widely in different individuals and diverged markedly from the ratio in the total γ-globulin of the individual. Two antibodies isolated from the serum of the same individual showed different ratios for the two groups.
Early death of mice cloned from somatic cells
Authors: Narumi Ogonuki, Kimiko Inoue, Yoshie Yamamoto, Yoko Noguchi, Kentaro Tanemura, Osamu Suzuki, Hiroyuki Nakayama, Kunio Doi, Yukiko Ohtomo, Michiko Satoh, Akira Nishida, Atsuo Ogura
Journal: Nature Genetics (2002)
Toll-like receptor mRNA levels in alveolar macrophages after inhalation of endotoxin
Authors: N. A. Maris, M. C. Dessing, A. F. de Vos, P. Bresser, J. S. van der Zee, H. M. Jansen, C. A. Spek, T. van der Poll
Journal: European Respiratory Journal (2006)

Toll-like receptors (TLRs) are pattern-recognition receptors that have been implicated in the initiation of innate immune responses upon the first encounter with invading pathogens. The airways are frequently exposed to various types of lipopolysaccharide (LPS) from the environment or from pathogens. The current study was designed to determine the effect of LPS on TLR gene expression in human alveolar macrophages in vivo . In total, 16 healthy subjects were enrolled in a single-blinded, placebo-controlled study. Subjects inhaled 100 μg LPS or normal saline (n = 8 per group). Measurements were performed in alveolar macrophages purified from bronchoalveolar lavage fluid obtained 6 h post-challenge. Inhalation of LPS by healthy human volunteers resulted in enhanced alveolar macrophage expression of mRNAs encoding TLRs 1, 2, 7, 8 and CD14, and reduced expression of mRNAs encoding TLR4 and lymphocyte antigen 96. In conclusion, lipopolysaccharide differentially influences the toll-like receptor mRNA expression profile in human alveolar macrophages in vivo .
Long-Term Effects of Ranirestat (AS-3201) on Peripheral Nerve Function in Patients With Diabetic Sensorimotor Polyneuropathy
Authors: Vera Bril, Robert A. Buchanan
Journal: Diabetes Care (2006)

OBJECTIVES—We aimed to determine whether ranirestat, an aldose reductase inhibitor, maintains the improved nerve function observed in patients with diabetic sensorimotor polyneuropathy (DSP) after completing a 12-week nerve biopsy study. RESEARCH DESIGN AND METHODS—Patients with mild to moderate DSP, as determined by the presence of sural nerve responses, were enrolled in a double-blind, placebo-controlled biopsy trial and randomized to placebo or 5 or 20 mg/day ranirestat for 12 weeks. Patients completing this biopsy study were offered a 48-week extension at the same ranirestat dose or at 5 mg/day ranirestat if they were originally treated with placebo. Electrophysiological tests, the Toronto Clinical Neuropathy Score, and vibration perception thresholds (VPTs) were performed at entry and at 12 (end of the biopsy study) and 60 (end of the 48-week extension) weeks. RESULTS—Peroneal motor nerve conduction velocity (NCV) improved in the 20-mg/day group following 60 weeks of treatment. Sural and median sensory NCV improved after both 12 and 60 weeks of treatment with 20 mg/day. VPT improved after 60 weeks of treatment with 20 mg/day. Ranirestat was well tolerated with no difference in adverse events between the 5- and 20-mg/day groups. CONCLUSIONS—Twenty milligrams ranirestat per day improves NCV and VPT following 60 weeks of administration. The improved sensory nerve function observed after 12 weeks of therapy was maintained at 60 weeks, and improved motor nerve function was observed at 60 weeks.
Ventilation heterogeneity is a major determinant of airway hyperresponsiveness in asthma, independent of airway inflammation
Authors: S. R Downie, C. M Salome, S. Verbanck, B. Thompson, N. Berend, G. G King
Journal: Thorax (2007)

<b>Background:</b> Airway hyperresponsiveness is the ability of airways to narrow excessively in response to inhaled stimuli and is a key feature of asthma. Airway inflammation and ventilation heterogeneity have been separately shown to be associated with airway hyperresponsiveness. A study was undertaken to establish whether ventilation heterogeneity is associated with airway hyperresponsiveness independently of airway inflammation in subjects with asthma and to determine the effect of inhaled corticosteroids on this relationship. <b>Methods:</b> Airway inflammation was measured in 40 subjects with asthma by exhaled nitric oxide, ventilation heterogeneity by multiple breath nitrogen washout and airway hyperresponsiveness by methacholine challenge. In 18 of these subjects with uncontrolled symptoms, measurements were repeated after 3 months of treatment with inhaled beclomethasone dipropionate. <b>Results:</b> At baseline, airway hyperresponsiveness was independently predicted by airway inflammation (partial r<sup>2</sup> = 0.20, p&lt;0.001) and ventilation heterogeneity (partial r<sup>2</sup> = 0.39, p&lt;0.001). Inhaled corticosteroid treatment decreased airway inflammation (p = 0.002), ventilation heterogeneity (p = 0.009) and airway hyperresponsiveness (p&lt;0.001). After treatment, ventilation heterogeneity was the sole predictor of airway hyperresponsiveness (r<sup>2</sup> = 0.64, p&lt;0.001). <b>Conclusions:</b> Baseline ventilation heterogeneity is a strong predictor of airway hyperresponsiveness, independent of airway inflammation in subjects with asthma. Its persistent relationship with airway hyperresponsiveness following anti-inflammatory treatment suggests that it is an important independent determinant of airway hyperresponsiveness. Normalisation of ventilation heterogeneity is therefore a potential goal of treatment that may lead to improved long-term outcomes.
Sports injury prevention: Mission Possible!
Authors: Hilde Moseby Berge, Ben Clarsen
Journal: British Journal of Sports Medicine (2013)

‘Mission completed’ could be the headline for Myklebust et al who tell the story of how the incidence of ACL injury among female handball players in Norway has been kept low, 10 years after the publication of their successful intervention study.1 An inspirational read, emphasising how a step-by-step approach combined with hard work and persistence, can make a difference (that matters). This issue highlights Norway's systematic, consistent and long-term approach to addressing key research areas: sports injury prevention, active rehabilitation, women's health and physical activity medicine. It also celebrates BJSM welcoming the Norwegian Association of Sports Medicine and Physical Activity (NIMF) and the Norwegian Sports Physiotherapy Association (FFI) as member societies; a partnership we are extremely proud of. Full text of BJSM is freely available to all Norwegian URL addresses, not just to society members.

Since the establishment of Oslo Sports Trauma Research Centre (OSTRC) 13 years ago, its members have contributed to over 200 articles covering the various stages of systematic injury prevention research (figure 1).2 ,3 Examples of …
Induction of Hemoglobin F Synthesis in Patients with β Thalassemia
Authors: T J Ley, A W Nienhuis
Journal: Annual Review of Medicine (1985)

5-Azacytidine transiently augments fetal hemoglobin production in patients with beta-thalassemia or sickle cell anemia. This change would probably be beneficial to such patients (e.g. a normal fetal gene product is substituted for a deficient or defective adult gene product) if HbF production could be sustained at high levels for prolonged periods. Even though the clinical use of 5-azacytidine is limited because of its presumed potential to cause cancer, studies with this drug have provided new insights into globin gene regulation and have stimulated the development of other strategies to increase HbF synthesis.
MicroRNA-661, a c/EBPα Target, Inhibits Metastatic Tumor Antigen 1 and Regulates Its Functions
Authors: Sirigiri Divijendra Natha Reddy, Suresh B. Pakala, Kazufumi Ohshiro, Suresh K. Rayala, Rakesh Kumar
Journal: Cancer Research (2009)

MicroRNAs (miR) have been identified as posttranscriptional modifiers of target gene regulation and control the expression of gene products important in cancer progression. Here, we show that miR-661 inhibits the expression of metastatic tumor antigen 1 (MTA1), a widely up-regulated gene product in human cancer, by targeting the 3' untranslated region (UTR) of MTA1 mRNA. We found that endogenous miR-661 expression was positively regulated by the c/EBPalpha transcription factor, which is down-regulated during cancer progression. c/EBPalpha directly interacted with the miR-661 chromatin and bound to miR-661 putative promoter that contains a c/EBPalpha-consensus motif. In addition, we found that the level of MTA1 protein was progressively up-regulated, whereas that of miR-661 and its activator, c/EBPalpha, were down-regulated in a breast cancer progression model consisting of MCF-10A cell lines whose phenotypes ranged from noninvasive to highly invasive. c/EBPalpha expression in breast cancer cells resulted in increased miR-661 expression and reduced MTA1 3'UTR-luciferase activity and MTA1 protein level. We also provide evidence that the introduction of miR-661 inhibited the motility, invasiveness, anchorage-independent growth, and tumorigenicity of invasive breast cancer cells. We believe our findings show for the first time that c/EBPalpha regulates the level of miR-661 and in turn modifies the functions of the miR661-MTA1 pathway in human cancer cells. Based on these findings, we suggest that miR-661 be further investigated for therapeutic use in down-regulating the expression of MTA1 in cancer cells.
Rifapentine, Moxifloxacin, or DNA Vaccine Improves Treatment of Latent Tuberculosis in a Mouse Model
Authors: Eric Nuermberger, Sandeep Tyagi, Kathy N. Williams, Ian Rosenthal, William R. Bishai, Jacques H. Grosset
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Priorities for developing improved regimens for treatment of latent tuberculosis (TB) infection include (1) developing shorter and/or more intermittently administered regimens that are easier to supervise and (2) developing and evaluating regimens that are active against multidrug-resistant organisms.Objectives and Methods: By using a previously validated murine model that involves immunizing mice with Mycobacterium bovis bacillus Calmette-Guérin to augment host immunity before infection with virulent Mycobacterium tuberculosis, we evaluated new treatment regimens including rifapentine and moxifloxacin, and assessed the potential of the Mycobacterium leprae heat shock protein-65 DNA vaccine to augment the activity of moxifloxacin.Measurements: Quantitative spleen colony-forming unit counts, and the proportion of mice with culture-positive relapse after treatment, were determined.Main Results: Three-month, once-weekly regimens of rifapentine combined with either isoniazid or moxifloxacin were as active as daily isoniazid for 6–9 mo. Six-month daily combinations of moxifloxacin with pyrazinamide, ethionamide, or ethambutol were more active than pyrazinamide plus ethambutol, a regimen recommended for latent TB infection after exposure to multidrug-resistant TB. The combination of moxifloxacin with the experimental nitroimidazopyran PA-824 was especially active. Finally, the heat shock protein-65 DNA vaccine had no effect on colony-forming unit counts when given alone, but augmented the bactericidal activity of moxifloxacin.Conclusions: Together, these findings suggest that rifapentine, moxifloxacin, and, perhaps, therapeutic DNA vaccination have the potential to improve on the current treatment of latent TB infection.
<i>BRCA1</i> Suppresses Epithelial-to-Mesenchymal Transition and Stem Cell Dedifferentiation during Mammary and Tumor Development
Authors: Feng Bai, Ho Lam Chan, Alexandria Scott, Matthew D. Smith, Cheng Fan, Jason I. Herschkowitz, Charles M. Perou, Alan S. Livingstone, David J. Robbins, Anthony J. Capobianco, Xin-Hai Pei
Journal: Cancer Research (2014)

BRCA1 mutation carriers are predisposed to developing basal-like breast cancers with high metastasis and poor prognosis. Yet, how BRCA1 suppresses formation of basal-like breast cancers is still obscure. Deletion of p18(Ink4c) (p18), an inhibitor of CDK4 and CDK6, functionally inactivates the RB pathway, stimulates mammary luminal stem cell (LSC) proliferation, and leads to spontaneous luminal tumor development. Alternately, germline mutation of Brca1 shifts the fate of luminal cells to cause luminal-to-basal mammary tumor transformation. Here, we report that disrupting Brca1 by either germline or epithelium-specific mutation in p18-deficient mice activates epithelial-to-mesenchymal transition (EMT) and induces dedifferentiation of LSCs, which associate closely with expansion of basal and cancer stem cells and formation of basal-like tumors. Mechanistically, BRCA1 bound to the TWIST promoter, suppressing its activity and inhibiting EMT in mammary tumor cells. In human luminal cancer cells, BRCA1 silencing was sufficient to activate TWIST and EMT and increase tumor formation. In parallel, TWIST expression and EMT features correlated inversely with BRCA1 expression in human breast cancers. Together, our findings showed that BRCA1 suppressed TWIST and EMT, inhibited LSC dedifferentiation, and repressed expansion of basal stem cells and basal-like tumors. Thus, our work offers the first genetic evidence that Brca1 directly suppresses EMT and LSC dedifferentiation during breast tumorigenesis.
STAT3-Dependent Mouse Embryonic Stem Cell Differentiation Into Cardiomyocytes
Authors: Johnson Rajasingh, Evelyn Bord, Hiromichi Hamada, Erin Lambers, Gangjian Qin, Douglas W. Losordo, Raj Kishore
Journal: Circulation Research (2007)

Pluripotent embryonic stem (ES) cell therapy may be an attractive source for postinfarction myocardial repair and regeneration. However, the specific stimuli and signal pathways that may control ES cell-mediated cardiomyogenesis remains to be completely defined. The aim of the present study was to investigate (1) the effect and underlying signal transduction pathways of leukemia inhibitory factor (LIF) and bone-morphogenic protein-2 (BMP-2)-induced mouse ES cell (mES-D3 line) differentiation into cardiomyocytes (CMC) and (2) the efficacy of CMC precommitted mES cells for functional and anatomical cardiac repair in surgically-induced mouse acute myocardial infarction (AMI) model. Various doses of LIF and BMP-2 and their inhibitors or blocking antibodies were tested for mES differentiation to CMC in vitro. CMC differentiation was assessed by mRNA and protein expression of CMC-specific markers, Connexin-43, CTI, CTT, Mef2c, Tbx5, Nkx2.5, GATA-4, and alphaMHC. LIF and BMP-2 synergistically induced the expression of CMC markers as early as 2 to 4 days in culture. Signaling studies identified STAT3 and MAP kinase (ERK1/2) as specific signaling components of LIF+BMP-2-mediated CMC differentiation. Inhibition of either STAT3 or MAPK activation by specific inhibitors drastically suppressed LIF+BMP-2-mediated CMC differentiation. Moreover, in mouse AMI, transplantation of lentivirus-GFP-transduced, LIF+BMP-2 precommitted mES cells, improved post-MI left ventricular functions, and enhanced capillary density. Transplanted cells engrafted in myocardium and differentiated into CMC and endothelial cells. Our data suggest that LIF and BMP-2 may synergistically enhance CMC differentiation of transplanted stem cells. Thus augmentation of LIF/BMP-2 downstream signaling components or cell type specific precommitment may facilitate the effects of ES cell-based therapies for post-MI myocardial repair and regeneration.
The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo
Authors: E ASHLEY, J POWERS, M CHEN, R KUNDU, T FINSTERBACH, A CAFFARELLI, A DENG, J EICHHORN, R MAHAJAN, R AGRAWAL
Journal: Cardiovascular Research (2004)

The endogenous peptide apelin is differentially regulated in cardiovascular disease but the nature of its role in cardiac function remains unclear.We investigated the functional relevance of this peptide using ECG and respiration gated magnetic resonance imaging, conductance catheter pressure-volume hemodynamic measurements, and echocardiography in vivo. In addition, we carried out histology and immunohistochemistry to assess cardiac hypertrophy and to localize apelin and APJ in the adult and embryonic mouse heart.Intraperitoneal injection of apelin (300 microg/kg) resulted in a decrease in left ventricular end diastolic area (pre: 0.122+/-0.007; post: 0.104+/-0.005 cm(2), p=0.006) and an increase in heart rate (pre: 537+/-20; post: 559+/-19 beats per minute, p=0.03). Hemodynamic measurements revealed a marked increase in ventricular elastance (pre: 3.7+/-0.9; post: 6.5+/-1.4 mm Hg/RVU, p=0.018) and preload recruitable stroke work (pre: 27.4+/-8.0; post: 51.8+/-3.1, p=0.059) with little change in diastolic parameters following acute infusion of apelin. Chronic infusion (2 mg/kg/day) resulted in significant increases in the velocity of circumferential shortening (baseline: 5.36+/-0.401; 14 days: 6.85+/-0.358 circ/s, p=0.049) and cardiac output (baseline: 0.142+/-0.019; 14 days: 0.25+/-0.019 l/min, p=0.001) as determined by 15 MHz echocardiography. Post-mortem corrected heart weights were not different between apelin and saline groups (p=0.5) and histology revealed no evidence of cellular hypertrophy in the apelin group (nuclei per unit area, p=0.9). Immunohistochemistry studies revealed APJ staining of myocardial cells in all regions of the adult mouse heart. Antibody staining, as well as quantitative real time polymerase chain reaction identified expression of both APJ and apelin in embryonic myocardium as early as embryonic day 13.5.Apelin reduces left ventricular preload and afterload and increases contractile reserve without evidence of hypertrophy. These results associate apelin with a positive hemodynamic profile and suggest it as an attractive target for pharmacotherapy in the setting of heart failure.
Siglec-5 and Siglec-14 are polymorphic paired receptors that modulate neutrophil and amnion signaling responses to group B <i>Streptococcus</i>
Authors: Syed Raza Ali, Jerry J. Fong, Aaron F. Carlin, Tamara D. Busch, Rebecka Linden, Takashi Angata, Thomas Areschoug, Mana Parast, Nissi Varki, Jeffrey Murray, Victor Nizet, Ajit Varki
Journal: The Journal of Experimental Medicine (2014)

Group B Streptococcus (GBS) causes invasive infections in human newborns. We recently showed that the GBS β-protein attenuates innate immune responses by binding to sialic acid–binding immunoglobulin-like lectin 5 (Siglec-5), an inhibitory receptor on phagocytes. Interestingly, neutrophils and monocytes also express Siglec-14, which has a ligand-binding domain almost identical to Siglec-5 but signals via an activating motif, raising the possibility that these are paired Siglec receptors that balance immune responses to pathogens. Here we show that β-protein–expressing GBS binds to both Siglec-5 and Siglec-14 on neutrophils and that the latter engagement counteracts pathogen-induced host immune suppression by activating p38 mitogen-activated protein kinase (MAPK) and AKT signaling pathways. Siglec-14 is absent from some humans because of a SIGLEC14-null polymorphism, and homozygous SIGLEC14-null neutrophils are more susceptible to GBS immune subversion. Finally, we report an unexpected human-specific expression of Siglec-5 and Siglec-14 on amniotic epithelium, the site of initial contact of invading GBS with the fetus. GBS amnion immune activation was likewise influenced by the SIGLEC14-null polymorphism. We provide initial evidence that the polymorphism could influence the risk of prematurity among human fetuses of mothers colonized with GBS. This first functionally proven example of a paired receptor system in the Siglec family has multiple implications for regulation of host immunity.
Effect of subintimal resection on initial outcome and restenosis for native coronary lesions and saphenous vein graft disease treated by directional coronary atherectomy A report from the Caveat I and II investigators
Authors: David R. Holmes, Kirk N. Garratt, Jeffrey M. Isner, Marianne Kearney, Lisa G. Berdan, Robert S. Schwartz, Robert M. Califf, Eric J. Topol
Journal: Journal of the American College of Cardiology (1996)
Reduced Heart Rate Variability Among Youth With Type 1 Diabetes
Authors: Mamta Jaiswal, Elaine M. Urbina, R. Paul Wadwa, Jennifer W. Talton, Ralph B. D’Agostino, Richard F. Hamman, Tasha E. Fingerlin, Stephen Daniels, Santica M. Marcovina, Lawrence M. Dolan, Dana Dabelea
Journal: Diabetes Care (2012)

OBJECTIVE This study compared heart rate variability (HRV) parameters in youth with and without type 1 diabetes and explored potential contributors of altered HRV. RESEARCH DESIGN AND METHODS HRV parameters were measured among 354 youth with type 1 diabetes (mean age 18.8 years, diabetes duration 9.8 years, and mean A1C 8.9%) and 176 youth without diabetes (mean age 19.2 years) participating in the SEARCH CVD study. Multiple linear regression was used to assess the relationship between diabetes status and HRV parameters, adjusting for covariates. RESULTS Compared with control subjects, youth with type 1 diabetes had reduced overall HRV (10.09 ms lower SD of NN intervals [SDNN]) and markers of parasympathetic loss (13.5 ms reduced root mean square successive difference of NN intervals [RMSSD] and 5.2 normalized units (n.u.) reduced high frequency [HF] power) with sympathetic override (5.2 n.u. increased low frequency [LF] power), independent of demographic, anthropometric, and traditional cardiovascular risk factors. Older age, female sex, higher LDL cholesterol and triglyceride levels, and presence of microalbuminuria were independently associated with lower HRV but did not account for the observed differences between youth with and without diabetes. Youth with type 1 diabetes and A1C levels ≥7.5% had significantly worse HRV parameters than control subjects; however, in youth with optimal glycemic control (A1C &amp;lt;7.5%), HRV parameters did not differ significantly from control subjects. CONCLUSIONS Youth with type 1 diabetes have signs of early cardiac autonomic neuropathy: reduced overall HRV and parasympathetic loss with sympathetic override. The main driver of these subclinical abnormalities appears to be hyperglycemia.
A Randomized Trial of Adenotonsillectomy for Childhood Sleep Apnea
Authors: Carole L. Marcus, Reneé H. Moore, Carol L. Rosen, Bruno Giordani, Susan L. Garetz, H. Gerry Taylor, Ron B. Mitchell, Raouf Amin, Eliot S. Katz, Raanan Arens, Shalini Paruthi, Hiren Muzumdar, David Gozal, Nina Hattiangadi Thomas, Janice Ware, Dean Beebe, Karen Snyder, Lisa Elden, Robert C. Sprecher, Paul Willging, Dwight Jones, John P. Bent, Timothy Hoban, Ronald D. Chervin, Susan S. Ellenberg, Susan Redline
Journal: New England Journal of Medicine (2013)

Adenotonsillectomy is commonly performed in children with the obstructive sleep apnea syndrome, yet its usefulness in reducing symptoms and improving cognition, behavior, quality of life, and polysomnographic findings has not been rigorously evaluated. We hypothesized that, in children with the obstructive sleep apnea syndrome without prolonged oxyhemoglobin desaturation, early adenotonsillectomy, as compared with watchful waiting with supportive care, would result in improved outcomes.