tbuckley/cabot-search huggingface dataset:
RANKL-induced DC-STAMP Is Essential for Osteoclastogenesis
Authors: Toshio Kukita, Naohisa Wada, Akiko Kukita, Takashi Kakimoto, Ferry Sandra, Kazuko Toh, Kengo Nagata, Tadahiko Iijima, Madoka Horiuchi, Hiromi Matsusaki, Kunio Hieshima, Osamu Yoshie, Hisayuki Nomiyama
Journal: The Journal of Experimental Medicine (2004)

Osteoclasts are bone-resorbing, multinucleated giant cells that are essential for bone remodeling and are formed through cell fusion of mononuclear precursor cells. Although receptor activator of nuclear factor–κB ligand (RANKL) has been demonstrated to be an important osteoclastogenic cytokine, the cell surface molecules involved in osteoclastogenesis are mostly unknown. Here, we report that the seven-transmembrane receptor-like molecule, dendritic cell–specific transmembrane protein (DC-STAMP) is involved in osteoclastogenesis. Expression of DC-STAMP is rapidly induced in osteoclast precursor cells by RANKL and other osteoclastogenic stimulations. Targeted inhibition of DC-STAMP by small interfering RNAs and specific antibody markedly suppressed the formation of multinucleated osteoclast-like cells. Overexpression of DC-STAMP enhanced osteoclastogenesis in the presence of RANKL. Furthermore, DC-STAMP directly induced the expression of the osteoclast marker tartrate-resistant acid phosphatase. These data demonstrate for the first time that DC-STAMP has an essential role in osteoclastogenesis.
Anti–DNA B Cells in MRL/lpr Mice Show Altered Differentiation and Editing Pattern
Authors: Yijin Li, Hui Li, Dongyao Ni, Martin Weigert
Journal: The Journal of Experimental Medicine (2002)

We have studied the regulation of anti–DNA B cells in transgenic mice with a heavy chain transgene (3H9H/56R). This transgene codes for a heavy chain that forms anti–double-stranded DNA (dsDNA) antibody when paired with most members of the endogenous Vκ repertoire, but certain L chains, referred to as Vκ editors, do not sustain dsDNA binding in combination with 3H9H/56R. In the nonautoimmune 3H9H/56R BALB/c, most B cells generated do not bind DNA because the transgene itself is edited or is associated with a Vκ editor. A minor population of B cells (30%) bind dsDNA and express the λ1 light chain (known to sustain 3H9H/56R DNA binding). These 3H9/56R/λ1 B cells coexpress a κ editor, and we propose that the down-regulation of the anti-DNA BCR caused by the dual L chain expression may prevent activation of this κ/λ population. These κ/λ B cells are sequestered in the marginal zone. Here, we studied the influence of autoimmunity on expression and regulation of 3H9H/56R. In 3H9H/56R MRL/lpr mice, the expression of anti-dsDNA is vastly accelerated. Anti–dsDNA B cells use noneditor κs but, in addition, most anti–dsDNA B cells have edited the heavy chain transgene. λ1 B cells (without the coexpression of a κ editor) are found and the κ/λ1 MZ population is absent. Our results suggest that improper editing and failure to sequester autoreactive B cells may contribute to the breakdown of tolerance in MRL/lpr mice.
Studies on Treatment of Acute Promyelocytic Leukemia With Arsenic Trioxide: Remission Induction, Follow-Up, and Molecular Monitoring in 11 Newly Diagnosed and 47 Relapsed Acute Promyelocytic Leukemia Patients
Authors: Chao Niu, Hua Yan, Ting Yu, Hui-Ping Sun, Jian-Xiang Liu, Xiu-Song Li, Wen Wu, Fen-Qin Zhang, Yu Chen, Li Zhou, Jun-Min Li, Xiao-Ying Zeng, Ren-Rong Ou Yang, Mi-Man Yuan, Mei-Yu Ren, Feng-Ying Gu, Qi Cao, Bo-Wei Gu, Xin-Ying Su, Guo-Qiang Chen, Shu-Min Xiong, Ting-dong Zhang, Samuel Waxman, Zhen-Yi Wang, Zhu Chen, Jiong Hu, Zhi-Xiang Shen, Sai-Juan Chen
Journal: Blood (1999)
Hormone Therapy and the Progression of Coronary-Artery Atherosclerosis in Postmenopausal Women
Authors: Howard N. Hodis, Wendy J. Mack, Stanley P. Azen, Roger A. Lobo, Donna Shoupe, Peter R. Mahrer, David P. Faxon, Linda Cashin-Hemphill, Miguel E. Sanmarco, William J. French, Thomas L. Shook, Thomas D. Gaarder, Anilkumar O. Mehra, Ramin Rabbani, Alex Sevanian, Asit B. Shil, Mina Torres, K. Heiner Vogelbach, Robert H. Selzer
Journal: New England Journal of Medicine (2003)

In postmenopausal women with coronary artery disease, conjugated equine estrogen with or without continuous administration of medroxyprogesterone acetate has failed to slow the progression of atherosclerosis. Whether 17β-estradiol (the endogenous estrogen molecule) alone or administered sequentially with medroxyprogesterone acetate can slow the progression of atherosclerosis is unknown.
Role of promoter hypermethylation in Cisplatin treatment response of male germ cell tumors.
Authors: Sanjay Koul, James M McKiernan, Gopeshwar Narayan, Jane Houldsworth, Jennifer Bacik, Deborah L Dobrzynski, Adel M Assaad, Mahesh Mansukhani, Victor E Reuter, George J Bosl, Raju SK Chaganti, Vundavalli VVS Murty
Journal: Molecular Cancer (2004)

Male germ cell tumor (GCT) is a highly curable malignancy, which exhibits exquisite sensitivity to cisplatin treatment. The genetic pathway(s) that determine the chemotherapy sensitivity in GCT remain largely unknown. We studied epigenetic changes in relation to cisplatin response by examining promoter hypermethylation in a cohort of resistant and sensitive GCTs. Here, we show that promoter hypermethylation of RASSF1A and HIC1 genes is associated with resistance. The promoter hypermethylation and/or the down-regulated expression of MGMT is seen in the majority of tumors. We hypothesize that these epigenetic alterations affecting MGMT play a major role in the exquisite sensitivity to cisplatin, characteristic of GCTs. We also demonstrate that cisplatin treatment induce de novo promoter hypermethylation in vivo. In addition, we show that the acquired cisplatin resistance in vitro alters the expression of specific genes and the highly resistant cells fail to reactivate gene expression after treatment to demethylating and histone deacetylase inhibiting agents. Our findings suggest that promoter hypermethylation of RASSF1A and HIC1 genes play a role in resistance of GCT, while the transcriptional inactivation of MGMT by epigenetic alterations confer exquisite sensitivity to cisplatin. These results also implicate defects in epigenetic pathways that regulate gene transcription in cisplatin resistant GCT.
Body size effects and rates of cytochrome b evolution in tube-nosed seabirds
Authors: G. B. Nunn, S. E. Stanley
Journal: Molecular Biology and Evolution (1998)

Variation in rates of molecular evolution now appears to be widespread. The demonstration that body size is correlated with rates of molecular evolution suggests that physiological and ecological factors may be involved in molecular rate variation, but large-scale comparative studies are still lacking. Here, we use complete cytochrome b sequences from 85 species of tube-nosed seabirds (order Procellariiformes) and 5 outgroup species of penguins (order Sphenisciformes) to test for an association between body mass and rates of molecular evolution within the former avian order. Cladistic analysis of the 90 sequences estimates a phylogeny largely consistent with the traditional taxonomy of the Procellariiformes. The Diomedeidae, Procellariidae, and Pelecanoididae are monophyletic, while the Hydrobatidae are basal and paraphyletic. However, the two subfamilies within the Hydrobatidae (Hydrobatinae and Oceanitinae) are monophyletic. A likelihood ratio test detects significant deviation from clocklike evolution in our data. Using a sign test for an association between body mass and branch length in the seabird phylogeny, we find that larger taxa tend to have shorter terminal branch lengths than smaller taxa. This observation suggests that rates of mitochondrial DNA evolution are slower for larger taxa. Rate calibrations based on the fossil record reveal concordant body size effects. We interpret these results as evidence for a metabolic rate effect, as the species in this order exhibit large differences in metabolic rates, which are known to be highly correlated with body mass in this group. Our results support previous findings of body size effects and show that this effect can be significant even within a single avian order. This suggests that even lineage-specific molecular clocks may not be tenable if calibrations involve taxa with different metabolic rates.
THE RATE OF REMOVAL OF RADIOACTIVE IRON FROM THE PLASMA—AN INDEX OF ERYTHROPOIESIS 1
Authors: Louis R. Wasserman, Ira A. Rashkoff, Dorothy Leavitt, Josephine Mayer, Shirley Port
Journal: Journal of Clinical Investigation (1952)

Transport iron normally exists in the plasma as ferric beta-l-globulinate. Since in most individuals the greater part of the body iron is incorporated in the hemoglobin of the red blood cells, it is probable that changes in the production and destruction of these erythrocytes will be reflected in the turnover of plasma iron. Radioactive iron of high specific activity is particularly useful for a study of iron metabolism since it can be injected intravenously in tracer amounts without changing the steady state of the organism; the turnover of this radioiron will then mirror the metabolism of the iron in the body.
Chronic Uremia Attenuates Growth Hormone–Induced Signal Transduction in Skeletal Muscle
Authors: Di Fei Sun, Zhilan Zheng, Padmaja Tummala, Jun Oh, Franz Schaefer, Ralph Rabkin
Journal: Journal of the American Society of Nephrology (2004)

Malnutrition and muscle wasting are common in chronic renal failure (CRF) and adversely affect morbidity and mortality. Contributing to the muscle wasting is resistance to growth hormone (GH). For testing whether impaired GH signaling is a cause of the skeletal muscle GH resistance and for elucidating its mechanisms, muscle GH signaling and action were studied in GH-deficient rats with surgically induced CRF and sham-operated pairfed control rats. GH treatment increased gastrocnemius muscle IGF-1 mRNA levels significantly in control but not in CRF rats. GH-activated Janus-associated kinase 2 (JAK2)-signal transducers and activators of transcription 5 (STAT5) signaling was impaired in CRF rats, despite normal GH receptor (GHR), JAK2, and STAT5 protein levels. Phosphorylation of the GHR, JAK2, and STAT5 in response to GH was depressed by nearly half in CRF (<i>P</i> &lt; 0.05), and nuclear phospho-STAT5 levels were depressed by approximately one third (<i>P</i> &lt; 0.01). GH-stimulated suppressors of cytokine signaling 2 mRNA levels were significantly higher in CRF. This may be related to inflammatory cytokine activity because C-reactive protein levels were elevated. Muscle protein-tyrosine phosphatase activity was also increased significantly by twofold. In conclusion, rats with CRF acquire skeletal muscle resistance to GH that is caused at least in part by impaired JAK2-GHR-STAT5 phosphorylation and nuclear STAT5 translocation. Furthermore, it seems that the attenuated JAK2-STAT5 phosphorylation may be caused by at least two different processes. One involves depressed phosphorylation of the signaling proteins because of increased suppressors of cytokine signaling 2 expression that may be linked to low-grade inflammation. The other may involve increased signaling protein dephosphorylation because of heightened protein-tyrosine phosphatase activity.
The Absence of Interleukin 1 Receptor–Related T1/St2 Does Not Affect T Helper Cell Type 2 Development and Its Effector Function
Authors: Katsuaki Hoshino, Shin-ichiro Kashiwamura, Kozo Kuribayashi, Taku Kodama, Tohru Tsujimura, Kenji Nakanishi, Tomohiro Matsuyama, Kiyoshi Takeda, Shizuo Akira
Journal: The Journal of Experimental Medicine (1999)

T1/ST2, an orphan receptor with homology with the interleukin (IL)-1 receptor family, is expressed constitutively and stably on the surface of T helper type 2 (Th2) cells, but not on Th1 cells. T1/ST2 is also expressed on mast cells, which are critical for Th2-mediated effector responses. To evaluate whether T1/ST2 is required for Th2 responses and mast cell function, we have generated T1/ST2-deficient (T1/ST2−/−) mice and examined the roles of T1/ST2. Naive CD4+ T cells isolated from T1/ST2−/− mice developed to Th2 cells in response to IL-4 in vitro. T1/ST2−/− mice showed normal Th2 responses after infection with the helminthic parasite Nippostrongylus brasiliensis as well as in the mouse model of allergen-induced airway inflammation. In addition, differentiation and function of bone marrow–derived cultured mast cells were unaffected. These findings demonstrate that T1/ST2 does not play an essential role in development and function of Th2 cells and mast cells.
Speciation of arsenic trioxide metabolites in peripheral blood and bone marrow from an acute promyelocytic leukemia patient
Authors: Noriyoshi Iriyama, Yuta Yoshino, Bo Yuan, Akira Horikoshi, Yukio Hirabayashi, Yoshihiro Hatta, Hiroo Toyoda, Jin Takeuchi
Journal: Journal of Hematology & Oncology (2012)

Speciation of arsenic trioxide (ATO) metabolites in clinical samples such as peripheral blood (PB) from acute promyelocytic leukemia (APL) patients has been conducted. However, speciation of arsenicals in bone marrow (BM) has not yet been performed. Profiles of arsenic speciation in plasma of BM were thus investigated and compared with those of PB plasma from a relapsed APL patient. The total arsenic concentrations in high molecular weight fraction (HMW-F) of BM and PB plasma were also determined.Response assessment was evaluated by BM aspirate examination and fluorescence in situ hybridization analysis. The analyses of total arsenic concentrations and speciation were preformed by inductively coupled plasma mass spectrometry (ICP-MS), and high-performance liquid chromatography (HPLC)/ICP-MS, respectively.Response assessment showed that the patient achieved complete remission. The total arsenic concentrations in BM plasma increased with time during the consecutive administration. The PB plasma concentrations of methylated arsenic metabolites substantially increased after the start of administration, while those of inorganic arsenic were still kept at a low level, followed by substantially increase from day-14 after administration. The arsenic speciation profiles of PB plasma were very similar to those of BM plasma. Furthermore, the total arsenic concentrations of HMW-F in BM plasma were much higher than those in PB plasma.The behaviors of arsenic speciation suggested for the first time that arsenic speciation analysis of PB plasma could be predicative for BM speciation, and showed relatively higher efficiency of drug metabolism in the patient. These results may further provide not only significance of clinical application of ATO, but also a new insight into host defense mechanisms in APL patients undergoing ATO treatment, since HMW proteins-bound arsenic complex could be thought to protect BM from the attack of free arsenic species.
Factors Associated With Weight Gain in People With Type 2 Diabetes Starting on Insulin
Authors: Beverley Balkau, Philip D. Home, Maya Vincent, Michel Marre, Nick Freemantle
Journal: Diabetes Care (2014)

Moderate weight gain is usual after starting insulin therapy. The identification and quantification of factors associated with weight gain may help target strategies for avoidance of weight gain.The noninterventional CREDIT (Cardiovascular Risk Evaluation in people with type 2 Diabetes on Insulin Therapy) study included data from people with type 2 diabetes starting any insulin in 314 centers, in 12 countries. From a number of predefined candidate explanatory variables, analyses identified factors associated with weight gain 1 year after starting insulin treatment, after adjusting for investigational site as a random factor. A multivariable backward regression analysis selected a subset of these factors associated with weight gain.We studied the 2,179 people with data for body weight change at 1 year and for potential predictive factors. The mean weight gain was 1.78 kg, and 24% gained ≥5.0 kg. Baseline factors associated with weight gain were BMI, A1C, insulin regimen, insulin dose, other glucose-lowering therapies, and hypertension; at 1 year, additional factors were A1C, insulin regimen, insulin dose, and use of other glucose-lowering therapies. In multivariable analysis, weight gain at 1 year was associated with a higher A1C at baseline, a higher insulin dose at baseline and at 1 year, and a lower baseline BMI.By the time insulin was started, a high baseline A1C and insulin dose requirements were independently associated with greater weight gain, as was lower baseline BMI. Insulin regimen per se was not a predictive factor.
Up-to-date monitoring of childhood cancer long-term survival in Europe: tumours of the sympathetic nervous system, retinoblastoma, renal and bone tumours, and soft tissue sarcomas
Authors: V. Arndt, B. Lacour, E. Steliarova-Foucher, C. Spix, A. Znaor, G. Pastore, C. Stiller, H. Brenner
Journal: Annals of Oncology (2007)
Isolation of a high molecular weight polyphosphate from Neisseria gonorrhoeae.
Authors: A Noegel, E C Gotschlich
Journal: The Journal of Experimental Medicine (1983)

Neisseria gonorrhoeae, as well as other Neisseriae, produce polyphosphate. This polyphosphate exists in two forms. Approximately half of it is loosely associated with the cells and can be recovered by washing in neutral buffers under conditions in which no significant lysis of the cells is observed. The other half is either intracellular or tightly associated, because it requires digestion of the cells with perchloric acid or sodium hypochlorite. Polyphosphate obtained by both methods was purified by column chromatography and chemically characterized. In contrast to other organisms, gonococci do not respond with increased polyphosphate synthesis when shifted from phosphate starvation to a phosphate-rich medium. In addition, gonococcal polyphosphate does not serve as a depletable phosphate source during phosphate starvation. All strains of Neisseriae examined produce substantial amounts of polyphosphate.
Analysis of Signal Transduction Pathways in Human Eosinophils Activated by Chemoattractants and the T-Helper 2–Derived Cytokines Interleukin-4 and Interleukin-5
Authors: Paul J. Coffer, René C. Schweizer, Gerald R. Dubois, Tjander Maikoe, Jan-Willem J. Lammers, Leo Koenderman
Journal: Blood (1998)
Remodeling of Gap Junctional Channel Function in Epicardial Border Zone of Healing Canine Infarcts
Authors: Jian-An Yao, Wajid Hussain, Pravina Patel, Nicholas S. Peters, Penelope A. Boyden, Andrew L. Wit
Journal: Circulation Research (2003)

The epicardial border zone (EBZ) of canine infarcts has increased anisotropy because of transverse conduction slowing. It remains unknown whether changes in gap junctional conductance (Gj) accompany the increased anisotropy. Ventricular cell pairs were isolated from EBZ and normal hearts (NZ). Dual patch clamp was used to quantify Gj. At a transjunctional voltage (Vj) of +10 mV, side-to-side Gj of EBZ pairs (9.2+/-3.4 nS, n=16) was reduced compared with NZ side-to-side Gj (109.4+/-23.6 nS, n=14, P<0.001). Gj of end-to-end coupled cells was not reduced in EBZ. Steady-state Gj of both NZ and EBZ showed voltage dependence, described by a two-way Boltzmann function. Half-maximal activation voltage in EBZ was shifted to higher Vj in positive and negative directions. Immunoconfocal planimetry and quantification showed no change in connexin43 per unit cell volume or surface area in EBZ. Decreased side-to-side coupling occurs in EBZ myocytes, independent of reduced connexin43 expression, and is hypothesized to contribute to increased anisotropy and reentrant arrhythmias.
Self-injury in Teenagers Who Lost a Parent to Cancer
Authors: Tove Bylund Grenklo, Ulrika Kreicbergs, Arna Hauksdóttir, Unnur A. Valdimarsdóttir, Tommy Nyberg, Gunnar Steineck, Carl Johan Fürst
Journal: JAMA Pediatrics (2012)

To investigate the risk of self-injury in parentally cancer-bereaved youth compared with their nonbereaved peers.Population-based study of cancer-bereaved youth and a random sample of matched population controls.Sweden in 2009 and 2010.A total of 952 youth (74.8%) confirmed to be eligible for the study returned the questionnaire: 622 (73.1%) of 851 eligible young adults who lost a parent to cancer between the ages of 13 and 16 years, in 2000 to 2003, and 330 (78.4%) of 451 nonbereaved peers.Cancer bereavement or nonbreavement during the teenage years.Unadjusted and adjusted odds ratios (ORs) of self-injury after January 1, 2000.Among cancer-bereaved youth, 120 (19.5%) reported self-injury compared with 35 (10.6%) of their nonbereaved peers, yielding an OR of 2.0 (95% CI, 1.4-3.0). After controlling for potential confounding factors in childhood (eg, having engaged in self-destructive behavior, having been bullied, having been sexually or physically abused, having no one to share joys and sorrows with, and sex), the adjusted OR was 2.3 (95% CI, 1.4-3.7). The OR for suicide attempts was 1.6 (95% CI, 0.8-3.0).One-fifth of cancer-bereaved youth reported self-injury, representing twice the odds for self-injury in their nonbereaved peers, regardless of any of the adjustments we made. Raised awareness on a broad basis in health care and allied disciplines would enable identification and support provision to this vulnerable group.
Computed Tomographic Analysis of the Anatomy of the Left Atrium and the Esophagus
Authors: Kristina Lemola, Michael Sneider, Benoit Desjardins, Ian Case, Jihn Han, Eric Good, Kamala Tamirisa, Ariane Tsemo, Aman Chugh, Frank Bogun, Frank Pelosi, Ella Kazerooni, Fred Morady, Hakan Oral
Journal: Circulation (2004)

During left atrial (LA) catheter ablation, an atrioesophageal fistula can develop as a result of thermal injury of the esophagus during ablation along the posterior LA. No in vivo studies have examined the relationship of the esophagus to the LA. The purpose of this study was to describe the topographic anatomy of the esophagus and the posterior LA by use of CT.A helical CT scan of the chest with 3D reconstruction was performed in 50 patients (mean age, 54+/-11 years) with atrial fibrillation before an ablation procedure. Consecutive axial and sagittal sections of the CT scan were examined to determine the relationship, size, and thickness of the tissue layers between the LA and the esophagus. The mean length and width of the esophagus in contact with the posterior LA were 58+/-14 and 13+/-6 mm, respectively. The esophagus had a variable course along the posterior LA. The esophagus was close (10+/-6 mm from the ostia) and parallel to the left-sided pulmonary veins (PVs) in 56% of patients and had an oblique course from the left superior PV to the right inferior PV in 36% of patients. The mean thicknesses of the posterior LA and anterior esophageal walls were 2.2+/-0.9 and 3.6+/-1.7 mm, respectively. In 98% of patients, there was a fat layer between the esophagus and the posterior LA. However, this layer was often discontinuous.The esophagus and posterior LA wall are in close contact over a large area that may often lie within the atrial fibrillation ablation zone, and there is marked variation in the anatomic relationship of the esophagus and the posterior LA. Both the esophageal and atrial walls are quite thin. However, a layer of adipose tissue may serve to insulate the esophagus from thermal injury, explaining why atrioesophageal fistulas are rare.