tbuckley/cabot-search huggingface dataset:
CELLULAR RECEPTORS: BINDING OF RADIOACTIVELY LABELED ANTI-ALLOANTISERUM
Authors: Hans Binz, Jean Lindenmann
Journal: The Journal of Experimental Medicine (1972)

RAT ALLOANTISERA OF THE FOLLOWING SPECIFICITIES WERE OBTAINED AFTER SINGLE SKIN GRAFT REJECTION: DA anti-BN, BN anti-DA, DA anti-Lewis, and Lewis anti-DA. Anti-alloantibodies were raised by injecting the first two alloantisera into (DA x BN)F(1) hosts and the last two alloantisera into (DA x Lewis)F(1) hosts. In this manner, four anti-alloantisera were raised: anti-(DA anti-BN), anti-(BN anti-DA), anti-(DA anti-Lewis), and anti-(Lewis anti-DA). From each anti-alloantiserum a gamma globulin fraction was prepared and trace labeled with (125)I. The labeled anti-alloantibodies could be shown to be fixed preferentially by red cells coated with the alloantibody used to induce them. They were also preferentially fixed by normal rat lymphoid cells presumed to carry recognition structures similar to alloantibody. For instance, anti-(DA anti-BN) was fixed by BN red cells coated with DA anti-BN and by normal DA lymphoid cells presumed to carry RS(BN). Conversely, anti-(BN anti-DA) was fixed by DA red cells coated with BN anti-DA and by normal BN lymphoid cells, carrying RS(DA). Absorption and inhibition experiments showed that alloantibodies and normal lymphoid cells compete for the same labeled anti-alloantibodies. We conclude that cellular receptors and circulating alloantibody are antigenically similar: They have the same aliotype.
412 ISOLATION AND DIFFERENTIATION OF BONE MARROW-DERIVED ENDOTHELIAL PROGENITOR CELLS IN PATIENTS WITH ADVANCED LIVER CIRRHOSIS FOR THERAPEUTICAL USE
Authors: V. Fernandez-Ruiz, D. D'Avola, M. Mendez, S. Carrillo, F. Prosper, J. Perez-Calvo, E. Andreu, S. Varea, J.I. Herrero, M. Inarrairaegui, B. Sangro, J. Prieto, J. Quiroga
Journal: Journal of Hepatology (2012)
Co58B12 absorption (hepatic surface count) after gastrectomy, ileal resection, and in coeliac disorders
Authors: D. J. Fone, W. T. Cooke, M. J. Meynell, E. L. Harris
Journal: Gut (1961)

This paper demonstrates that the hepatic surface counting technique is a reliable and satisfactory method of estimating the absorption of radioactive vitamin B(12). It does not require the collection of faeces or urine and is therefore particularly useful in studying out-patients.
Minimal residual disease-directed therapy for childhood acute myeloid leukaemia: results of the AML02 multicentre trial
Authors: Jeffrey E Rubnitz, Hiroto Inaba, Gary Dahl, Raul C Ribeiro, W Paul Bowman, Jeffrey Taub, Stanley Pounds, Bassem I Razzouk, Norman J Lacayo, Xueyuan Cao, Soheil Meshinchi, Barbara Degar, Gladstone Airewele, Susana C Raimondi, Mihaela Onciu, Elaine Coustan-Smith, James R Downing, Wing Leung, Ching-Hon Pui, Dario Campana
Journal: The Lancet Oncology (2010)
A SUCCESSFUL CASE OF HYSTERECTOMY FOR PUERPERAL INFECTION
Authors: A. K. Gordon
Journal: BMJ (1909)

HYSTERECTOMY'FOR PUERPERAL INFECTION. 'IJ I429In spite of our fears to the contrary, she went to term, and when she came into a nursing home on January 20th I was delighted to find her in very fair condition and free from serious symptoms.There could, however, be no doubt as to treatment, for the head was mobile above the pelvis, and could not be made to enter it, while a large, solid tumour occupied the pelvis and could not be pushed up.The liquor amnii began to be discharged on January 21st.
Genetic Variants and Family History Predict Prostate Cancer Similar to Prostate-Specific Antigen
Authors: S. Lilly Zheng, Jielin Sun, Fredrik Wiklund, Zhengrong Gao, Pär Stattin, Lina D. Purcell, Hans-Olov Adami, Fang-Chi Hsu, Yi Zhu, Jan Adolfsson, Jan-Erik Johansson, Aubrey R. Turner, Tamara S. Adams, Wennuan Liu, David Duggan, John D. Carpten, Bao-Li Chang, William B. Isaacs, Jianfeng Xu, Henrik Grönberg
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Although prostate-specific antigen (PSA) is the best biomarker for predicting prostate cancer, its predictive performance needs to be improved. Results from the Prostate Cancer Prevention Trial revealed the overall performance measured by the areas under curve of the receiver operating characteristic at 0.68. The goal of the present study is to assess the ability of genetic variants as a PSA-independent method to predict prostate cancer risk. Experimental Design: We systematically evaluated all prostate cancer risk variants that were identified from genome-wide association studies during the past year in a large population-based prostate cancer case-control study population in Sweden, including 2,893 prostate cancer patients and 1,781 men without prostate cancer. Results: Twelve single nucleotide polymorphisms were independently associated with prostate cancer risk in this Swedish study population. Using a cutoff of any 11 risk alleles or family history, the sensitivity and specificity for predicting prostate cancer were 0.25 and 0.86, respectively. The overall predictive performance of prostate cancer using genetic variants, family history, and age, measured by areas under curve was 0.65 (95% confidence interval, 0.63-0.66), significantly improved over that of family history and age (0.61%; 95% confidence interval, 0.59-0.62; P = 2.3 × 10−10). Conclusion: The predictive performance for prostate cancer using genetic variants and family history is similar to that of PSA. The utility of genetic testing, alone and in combination with PSA levels, should be evaluated in large studies such as the European Randomized Study for Prostate Cancer trial and Prostate Cancer Prevention Trial.
Speeding up the Evaluation of New Agents in Cancer
Authors: M. K. B. Parmar, F. M.- S. Barthel, M. Sydes, R. Langley, R. Kaplan, E. Eisenhauer, M. Brady, N. James, M. A. Bookman, A.-M. Swart, W. Qian, P. Royston
Journal: JNCI Journal of the National Cancer Institute (2008)

Despite both the increase in basic biologic knowledge and the fact that many new agents have reached various stages of development during the last 10 years, the number of new treatments that have been approved for patients has not increased as expected. We propose the multi-arm, multi-stage trial design as a way to evaluate treatments faster and more efficiently than current standard trial designs. By using intermediate outcomes and testing a number of new agents (and combinations) simultaneously, the new design requires fewer patients. Three trials using this methodology are presented.
Optical Mapping Reveals That Repolarization Spreads Anisotropically and Is Guided by Fiber Orientation in Guinea Pig Hearts
Authors: Anthony Kanai, Guy Salama
Journal: Circulation Research (1995)

Abstract Guinea pig hearts were stained with a voltage-sensitive dye and imaged on a photodiode array to record fluorescent action potentials (APs) from 124 sites. Activation and repolarization patterns were recorded from the epicardium during stimulation at different loci and correlated with the underlying fiber architecture. Endocardial APs were recorded by inserting a light guide into the ventricular cavity or by dissecting out the ventricular free wall to expose the endocardium. In hearts paced on the right atrium to simulate sinus rhythm, activation emerged synchronously over a large area of the ventricular epicardium and spread laterally in 5 to 7 ms. The apparent longitudinal and transverse velocities were 2.66±0.11 and 1.65±0.09 m/s (n=12). In contrast, repolarization began near the apex on the endocardium and spread transmurally in 6±1.3 ms (n=12) and then anisotropically along the epicardium in 25 to 30 ms with apparent maximum (0.53±0.11 m/s) and minimum (0.31±0.10 m/s) repolarization velocities that aligned with the longitudinal and transverse axes of epicardial fibers. When paced on the epicardium, activation of intact hearts (n=12) and perfused sheets (n=8) was anisotropic, with longitudinal (0.85±0.05 m/s) and transverse (0.44±0.04 m/s) conduction velocities that aligned with the epicardial fiber orientation. When activation was initiated at different sites on the epicardium, repolarization always began near the apex and exhibited patterns similar to those obtained under right atrial pacing, but with slower longitudinal (0.41±0.09 m/s) and transverse (0.23±0.07 m/s) repolarization velocities (n=18). In sheets stretched parallel to the longitudinal axis of surface fibers, AP durations (APDs) increased as a function of fiber length, from the length at zero developed tension to 120% of the length at maximum developed tension (L max ). Spatial distributions of APDs did not change during stretches along the rising phase of the length-tension curve. In sheets stretched to 50% of L max , APDs were shorter and more homogeneous on the endocardium (mean APD, 188 ms; ΔAPD, 195−186=9 ms) than on the epicardium (mean APD, 204 ms; ΔAPD, 212−186=26 ms; n=8). In guinea pig hearts, activation is rapid; therefore, repolarization depends primarily on intrinsic spatial heterogeneities of APDs. Consequently, repolarization begins at endocardial cells with the shortest APDs and spreads transmurally and then anisotropically on the surface according to the epicardial cell orientation.
High Incidence and Characterization of Glucocorticoid Receptors in Human Malignant Melanoma&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;,&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: H S Bhakoo, R J Milholland, R Lopez, C Karakousis, F Rosen
Journal: JNCI Journal of the National Cancer Institute (1981)

The glucocorticoid receptor was characterized in biopsy samples from patients with recurrent malignant melanoma. Glucocorticoid receptors were measured by the charcoaladsorption technique. Tumor cytosol from approximately 86% (25/29) of the patients contained large quantities of receptors (20-324 fmol/mg protein). The dissociation constant of this cytoplasmic receptor was determined to be 2-22 nM. This binding component sedimented at 7.15 on sucrose gradients of low ionic strength and dissociated into lower molecular weight components that sedimented at 4.45 on sucrose gradients of high ionic strength. Receptor binding was specific for glucocorticoids. Although progestins competed well for the binding that is typical for glycocorticoid receptor as reported in the literature, other steroids, e.g 17β-estradiol and 5α-dihydrotestosterone, were only weak competitors. These results demonstrated that this neoplasm contains large quantities of glucocorticoid receptors that are similar in their physicochemical characteristics to those found in normal tissues. This finding in human melanoma biopsy specimens may be of therapeutic value in the management of patients with malignant melanoma.
Pretreatment synovial transcriptional profile is associated with early and late clinical response in rheumatoid arthritis patients treated with rituximab
Authors: Vanessa E Hogan, Cécile T J Holweg, David F Choy, Sarah K Kummerfeld, Jason A Hackney, Y K Onno Teng, Michael J Townsend, Jacob M vanLaar
Journal: Annals of the Rheumatic Diseases (2012)

Personalised healthcare is contingent on the identification of biomarkers that represent disease relevant pathways and predict drug response. The authors aimed to develop a gene expression signature in synovial tissue that could enrich clinical response of rheumatoid arthritis (RA) patients to rituximab.The authors studied synovial gene expression using high-throughput quantitative real-time-PCR in 20 RA patients who underwent arthroscopy before and after treatment with rituximab. Several objective approaches were used to explore patterns in the data and to find genes associated with changes in disease activity due to treatment.This analysis revealed two patient populations associated with distinct clinical, laboratory and histological features and, importantly, showed enrichment for response (60% non-responders vs 90% responders). A composite baseline gene score (GS) correlated with change in disease activity score (ΔDAS) between baseline and month 3 (r=0.74, p=0.0002), but also with ΔDAS at later time-points (month 9, r=0.54, p=0.016; month 15, r=0.45, p=0.06; month 21, r=0.72, p=0.003). Notably, the GS significantly correlated with baseline erythrocyte sedimentation rate (r=0.69, p=0.0008), but not with other DAS components. The GS genes represented T cell, macrophage, remodelling and interferon-α biology. Responders demonstrated higher expression of macrophage and T cell genes, while non-responders showed higher expression of interferon-α and remodelling genes.This study reveals a baseline synovial GS that correlates with early and late clinical responses to rituximab. The GS biology suggests that T cells and macrophages are important for response to B cell depleting therapy, while expression of remodelling and interferon-α genes correlates with poor response.
Casein Kinase 2–Interacting Protein-1, a Novel Akt Pleckstrin Homology Domain-Interacting Protein, Down-regulates PI3K/Akt Signaling and Suppresses Tumor Growth <i>In vivo</i>
Authors: Emi Tokuda, Naoya Fujita, Tomoko Oh-hara, Shigeo Sato, Atsuo Kurata, Ryohei Katayama, Toshiki Itoh, Tadaomi Takenawa, Kohei Miyazono, Takashi Tsuruo
Journal: Cancer Research (2007)

The serine/threonine kinase Akt plays a central role in cell survival and proliferation. Its activation is linked to tumorigenesis in several human cancers. Although many Akt substrates have been elucidated, the Akt-binding proteins that regulate Akt function remain unclear. We report herein having identified casein kinase 2-interacting protein-1 (CKIP-1) as an Akt pleckstrin homology (PH) domain-binding protein with Akt inhibitory function. CKIP-1 formed a complex with each Akt isoform (Akt1, Akt2, and Akt3) via its NH2 terminus. Dimerization of CKIP-1 via its leucine zipper (LZ) motif at the COOH terminus was found to be associated with Akt inactivation because deletion of the LZ motif eliminated Akt inhibitory function, although it could still bind to Akt. Expression of the NH2 terminus-deleted CKIP-1 mutant containing the LZ motif, but lacking Akt-binding ability, induced Akt phosphorylation and activation by sequestering the ability of endogenous CKIP-1 to bind to Akt. Stable CKIP-1 expression caused Akt inactivation and cell growth inhibition in vitro. In addition, the growth of stable CKIP-1 transfectants xenografted into nude mice was slower than that of mock transfectants. These results indicate that CKIP-1, a novel Akt PH domain-interacting protein, would be a candidate of tumor suppressor with an Akt inhibitory function.
Genetic ablation of complement C3 attenuates muscle pathology in dysferlin-deficient mice
Authors: Renzhi Han, Ellie M. Frett, Jennifer R. Levy, Erik P. Rader, John D. Lueck, Dimple Bansal, Steven A. Moore, Rainer Ng, Daniel Beltrán-Valero de Bernabé, John A. Faulkner, Kevin P. Campbell
Journal: Journal of Clinical Investigation (2010)

Mutations in the dysferlin gene underlie a group of autosomal recessive muscle-wasting disorders denoted as dysferlinopathies. Dysferlin has been shown to play roles in muscle membrane repair and muscle regeneration, both of which require vesicle-membrane fusion. However, the mechanism by which muscle becomes dystrophic in these disorders remains poorly understood. Although muscle inflammation is widely recognized in dysferlinopathy and dysferlin is expressed in immune cells, the contribution of the immune system to the pathology of dysferlinopathy remains to be fully explored. Here, we show that the complement system plays an important role in muscle pathology in dysferlinopathy. Dysferlin deficiency led to increased expression of complement factors in muscle, while muscle-specific transgenic expression of dysferlin normalized the expression of complement factors and eliminated the dystrophic phenotype present in dysferlin-null mice. Furthermore, genetic disruption of the central component (C3) of the complement system ameliorated muscle pathology in dysferlin-deficient mice but had no significant beneficial effect in a genetically distinct model of muscular dystrophy, mdx mice. These results demonstrate that complement-mediated muscle injury is central to the pathogenesis of dysferlinopathy and suggest that targeting the complement system might serve as a therapeutic approach for this disease.
Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods
Authors: S.K. Weiland, B. Björkstén, B. Brunekreef, W.O.C. Cookson, E. von Mutius, D.P. Strachan
Journal: European Respiratory Journal (2004)

International comparative studies, investigating whether disease incidence or prevalence rates differ between populations and, if so, which factors explain the observed differences, have made important contributions to the understanding of disease aetiology in many areas. In Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence rates of symptoms of asthma, allergic rhinitis and atopic eczema in 13–14-yr-olds, assessed by standardised questionnaires, were found to differ &gt;20-fold between the 155 study centres around the world. Phase II of ISAAC aims to identify determinants of these differences by studying informative populations. A detailed study protocol was developed for use in community-based random samples of children aged 9–11 yrs. The study modules include standardised questionnaires with detailed questions on the occurrence and severity of symptoms of asthma, allergic rhinitis and atopic eczema, their clinical management, and a broad range of previous and current exposure conditions. In addition, standardised protocols were applied for examination of flexural dermatitis, skin-prick testing, bronchial challenge with hypertonic saline, blood sampling for immunoglobulin E analyses and genotyping, and dust sampling for assessment of indoor exposures to allergens and endotoxin. To date, ISAAC II field work had been completed or started in 30 study centres in 22 countries. The majority of centres are in countries that participated in International Study of Asthma and Allergies in Childhood Phase I and reflect almost the full range of the observed variability in Phase I prevalence rates.
Osteonecrosis in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Nina S. Kadan-Lottick, Irina Dinu, Karen Wasilewski-Masker, Sue Kaste, Lillian R. Meacham, Anita Mahajan, Marilyn Stovall, Yutaka Yasui, Leslie L. Robison, Charles A. Sklar
Journal: Journal of Clinical Oncology (2008)

Osteonecrosis (ON) is a potentially serious complication of therapy in survivors of childhood cancer. Our goals were to describe the incidence of ON and identify patient and treatment characteristics associated with elevated risk.The rate of self-reported ON was determined for 9,261 patients enrolled onto the Childhood Cancer Survivor Study, a cohort of 5-year survivors of childhood cancer diagnosed from 1970 to 1986, and compared with the rate in a random sample of 2,872 siblings of survivors. Survivors with positive responses were reinterviewed to confirm the diagnosis.Fifty-two cancer survivors reported ON in 78 joints, yielding 20-year cumulative incidence of 0.43% and a rate ratio (RR) of 6.2 (95% CI, 2.3 to 17.2) compared with siblings, adjusted for age and sex; 44% developed ON in a previous radiation field. The RR was greatest among survivors of stem-cell transplantation for acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (RR = 26.9, 66.5, and 93.1, respectively). Nontransplantation patients with ALL (RR = 6.5; 95% CI, 2.2 to 19.4), AML (RR = 11.2; 95% CI, 2.1 to 61.2), and bone sarcoma (RR = 7.3; 95% CI, 2.0 to 26.2) were at higher risk for ON. Older age at diagnosis, shorter elapsed time, older treatment era, exposure to dexamethasone (+/- prednisone), and gonadal and nongonadal radiation were independently associated with ON.ON among long-term survivors of childhood cancer is rare. However, compared with siblings, childhood cancer survivors have a significantly increased relative rate of ON, particularly those who were older at diagnosis and who received dexamethasone or radiation therapy. Future studies are needed to better delineate our findings, particularly the increased risk after gonadal radiation.
Stanniocalcin 1 and Ovarian Tumorigenesis
Authors: Guangzhi Liu, Gong Yang, Bin Chang, Imelda Mercado-Uribe, Miao Huang, Jingfang Zheng, Robert C. Bast, Sue-Hwa Lin, Jinsong Liu
Journal: JNCI Journal of the National Cancer Institute (2010)

Stanniocalcin 1 (STC1) is a secreted glycoprotein hormone. High expression of STC1 has been associated with several cancers including ovarian cancer, but its role in the development of ovarian cancer is not clear. We used five human ovarian epithelial cancer cell lines (OVCA420, OVCA432, OVCA433, SKOV3, and HEY), immortalized human ovarian surface epithelial cells (T29 and T80), ovarian cancer tissues from 342 patients, serum from 73 ovarian cancer patients and from58 control subjects, and 116 mice, with six or eight per group. Protein expression was assessed. Cells overexpressing STC1 protein were generated by ectopic expression of human STC1 cDNA. STC1 expression was silenced by using small interfering RNA against STC1. Cell proliferation, migration, colony formation, and apoptosis were assessed. Xenograft tumor growth in mice was studied. Neutralizing anti-STC1 antibody was used to inhibit STC1 function. All statistical tests were two-sided. STC1 protein expression was higher in all human ovarian cancer cell lines examined than in immortalized human ovarian epithelial cell lines, higher in ovarian cancer tissue than in normal ovarian tissue (P < .001), and higher in serum from ovarian cancer patients than from control subjects (P = .021). Ovarian cancer cells with STC1 overexpression, compared with corresponding control cells, had increased cell proliferation, migration, and colony formation in cell culture and increased growth of xenograft tumors in mice. These activities in normal or malignant ovarian cells with STC1 overexpression, compared with control cells, were also accompanied by increased expression of cell cycle regulatory proteins and antiapoptotic proteins but decreased cleavage of several caspases. Within 24 hours of treatment, apoptosis in cultures of HEY ovarian cancer cells treated with neutralizing anti-STC1 monoclonal antibody was higher (17.3% apoptotic cells) than that in cultures treated with mouse IgG control cells (4.4%) (12.9% difference, 95% confidence interval = 11.6% to 14.2%). STC1 protein may be involved in ovarian tumorigenesis.
Autophagy is involved in oligodendroglial precursor-mediated clearance of amyloid peptide
Authors: Wenxia Li, Yifen Tang, Zhiqin Fan, Ya Meng, Guang Yang, Jia Luo, Zun-Ji Ke
Journal: Molecular Neurodegeneration (2013)

Accumulation of β-amyloid peptides is an important hallmark of Alzheimer's disease (AD). Tremendous efforts have been directed to elucidate the mechanisms of β-amyloid peptides degradation and develop strategies to remove β-amyloid accumulation. In this study, we demonstrated that a subpopulation of oligodendroglial precursor cells, also called NG2 cells, were a new cell type that can clear β-amyloid peptides in the AD transgene mice and in NG2 cell line.NG2 cells were recruited and clustered around the amyloid plaque in the APPswe/PS1dE9 mice, which is Alzheimer's disease mouse model. In vitro, NG2 cell line and primary NG2 cells engulfed β-amyloid peptides through the mechanisms of endocytosis in a time dependent manner. Endocytosis is divided into pinocytosis and phagocytosis. Aβ(42) internalization by NG2 cells was mediated by actin-dependent macropinocytosis. The presence of β-amyloid peptides stimulated the autophagic pathway in NG2 cells. Once inside the cells, the β-amyloid peptides in NG2 cells were transported to lysosomes and degraded by autophagy.Our findings suggest that NG2 cells are a new cell type that can clear β-amyloid peptides through endocytosis and autophagy.