tbuckley/cabot-search huggingface dataset:
A Controlled Trial To Increase Detection and Treatment of Osteoporosis in Older Patients with a Wrist Fracture
Authors: Sumit R. Majumdar, Brian H. Rowe, Deb Folk, Jeffrey A. Johnson, Brian H. Holroyd, Donald W. Morrish, Walter P. Maksymowych, Ivan P. Steiner, Charles H. Harley, Brian J. Wirzba, David A. Hanley, Sandra Blitz, Anthony S. Russell
Journal: Annals of Internal Medicine (2004)

Despite the high risk for future fractures and the availability of effective treatments, fewer than 10% to 20% of patients who sustain a fragility fracture are tested or treated for osteoporosis.
ITGAM coding variant (rs1143679) influences the risk of renal disease, discoid rash and immunological manifestations in patients with systemic lupus erythematosus with European ancestry
Authors: X. Kim-Howard, A. K. Maiti, J.-M. Anaya, G. R. Bruner, E. Brown, J. T. Merrill, J. C. Edberg, M. A. Petri, J. D. Reveille, R. Ramsey-Goldman, G. S. Alarcon, T. J. Vyse, G. Gilkeson, R. P. Kimberly, J. A. James, J. M. Guthridge, J. B. Harley, S. K. Nath
Journal: Annals of the Rheumatic Diseases (2009)

<h3>Purpose</h3> It was hypothesised that the coding variant (R77H), rs1143679, within ITGAM could predict specific clinical manifestations associated with systemic lupus erythematosus (SLE). <h3>Method</h3> To assess genetic association, 2366 patients with SLE and 2931 unaffected controls with European ancestry were analysed. The patients with SLE were coded by the presence or absence of individual American College of Rheumatology criteria. Logistic regression and Pearson χ<sup>2</sup> tests were used to assess statistical significance. <h3>Results</h3> For overall case-control analysis, a highly significant association was detected (p=2.22×10−21, OR 1.73). Using case-only analysis, a significant association was detected with renal criteria (p=0.0003), discoid rash (p=0.02) and immunological criteria (p=0.04). When patients with SLE were compared with healthy controls, the association became stronger for renal (p=4.69×10−22, OR 2.15), discoid (p=1.77×10−14, OR 2.03) and immunological (p=3.49×10−22, OR 1.86) criteria. Risk allele frequency increased from 10.6% (controls) to 17.0% (SLE), 20.4% (renal), 18.1% (immunological) and 19.5% (discoid). <h3>Conclusion</h3> These results show a strong association between the risk allele (A) at rs1143679 and renal disease, discoid rash and immunological manifestations of SLE.
An Insertion/Deletion Polymorphism within RERT-lncRNA Modulates Hepatocellular Carcinoma Risk
Authors: Zhansheng Zhu, Xueren Gao, Yan He, Hua Zhao, Qiang Yu, Deke Jiang, Pingzhao Zhang, Xiaopin Ma, Huixing Huang, Dong Dong, Jiao Wan, Zhenyong Gu, Xinghong Jiang, Long Yu, Yuzhen Gao
Journal: Cancer Research (2012)

The Prolyl hydroxylase 1 (EGLN2) is known to affect tumorigenesis by regulating the degradation of hypoxia-inducible factor. Polymorphisms in EGLN2 may facilitate cancer cell survival under hypoxic conditions and directly associate with cancer susceptibility. Here, we examined the contribution of a 4-bp insertion/deletion polymorphism (rs10680577) within the distal promoter of EGLN2 to the risk of hepatocelluar carcinoma (HCC) in Chinese populations. The contribution of rs10680577 to HCC risk was investigated in 623 HCC cases and 1,242 controls and replicated in an independent case-control study consisting of 444 HCC cases and 450 controls. Logistic regression analysis showed that the deletion allele of rs10680577 was significantly associated with increased risk for HCC occurrence in both case-control studies [OR = 1.40; 95% confidence interval (CI) = 1.18-1.66, P < 0.0001; OR = 1.49; 95% CI = 1.18-1.88, P = 0.0007]. Such positive association was more pronounced in current smokers (OR = 3.49, 95% CI = 2.24-5.45) than nonsmokers (OR = 1.24, 95% CI = 1.03-1.50; heterogeneity P = 0.0002). Genotype-phenotype correlation studies showed that the deletion allele was significantly correlated with higher expression of both EGLN2 and RERT-lncRNA [a long noncoding RNA whose sequence overlaps with Ras-related GTP-binding protein 4b (RAB4B) and EGLN2)] in vivo and in vitro. Furthermore, RERT-lncRNA expression was also significantly correlated with EGLN2 expression in vivo, consistent with in vitro gain-of-function study that showed overexpressing RERT-lncRNA upregulated EGLN2. Finally, in silico prediction suggested that the insertion allele could disrupt the structure of RERT-lncRNA. Taken together, our findings provided strong evidence for the hypothesis that rs10680577 contributes to hepatocarcinogenesis, possibly by affecting RERT-lncRNA structure and subsequently EGLN2 expression, making it a promising biomarker for early diagnosis of HCC.
BLOCKAGE OF AMYLOID INDUCTION BY COLCHICINE IN AN ANIMAL MODEL
Authors: Tsuranobu Shirahama, Alan S. Cohen
Journal: The Journal of Experimental Medicine (1974)

Colchicine was found to have a strong inhibitory effect on amyloid induction in an animal model. When CBA/J mice were treated with colchicine concurrently with the amyloid induction regimen, the incidence of amyloidosis was, depending upon the dosage of colchicine, significantly decreased (0.005-0.010 mg colchicine per day) or completely blocked (more than 0.015 mg colchicine per day). The colchicine treatment was effective not only when colchicine was given for the entire course of the amyloid induction regimen but also when it was given only in the late pre-amyloid or the amyloid phase of the regimen or to the recipients after the transfer of amyloid. The data suggest the colchicine is effective in blocking amyloidogenesis at its final stage(s), while it may not affect significantly amyloid already deposited in the tissue.
Rituximab-Mediated Cell Signaling and Chemo/Immuno-sensitization of Drug-Resistant B-NHL Is Independent of Its Fc Functions
Authors: Mario I. Vega, Sara Huerta-Yepez, Melisa Martinez-Paniagua, Bernardo Martinez-Miguel, Rogelio Hernandez-Pando, Cesar R. González-Bonilla, Paul Chinn, Nabil Hanna, Kandasamy Hariharan, Ali R. Jazirehi, Benjamin Bonavida
Journal: Clinical Cancer Research (2009)

Rituximab [chimeric anti-CD20 monoclonal antibody], alone or combined with chemotherapy, is used in the treatment of non-Hodgkin's lymphoma (NHL). Rituximab binds to CD20 and inhibits intracellular survival/growth pathways leading to chemo/immunosensitization of tumor cells in vitro. The contribution of rituximab Fc-FcR interaction in signaling is not known. This study examined the role of Fc-FcR interactions in rituximab-induced signaling using rituximab (Fab')(2) fragments as well as rituximab devoid of the CH2 Fc-binding domain (CH2(-)).Rituximab (CH2(-)) and rituximab (Fab')(2) were tested for their activity on B-NHL cell lines. Cell signaling and sensitization to chemotherapy and immunotherapy were examined. The in vitro studies were validated in mice bearing tumor xenografts.Although the modified antibodies were defective in antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity functions, they retained all other biological activities such as inhibition of cell proliferation, induction of cell aggregation, and apoptosis induction. In addition, similar to rituximab, the modified antibodies inhibited the activity of cell survival/growth pathways and their associated transcription factors (e.g., NF-kappaB, YY1, SP-1), and signal transducers and activators of transcription 3 (STAT-3), and downregulated the expression of antiapoptotic gene products, such as Bcl-2/Bcl(xl), which regulate drug resistance. The modified antibodies, similar to rituximab, sensitized resistant B-NHL cells to both CDDP and Fas ligand-induced apoptosis. Furthermore, treatment of nude mice bearing Raji tumor cell xenografts with the combination of rituximab (Fab')(2) or rituximab and CDDP resulted in similar and significant inhibition of tumor growth.These findings reveal that rituximab-mediated inhibition of intracellular signaling pathways and leading to chemo/immuno-sensitization of resistant B-NHL is Fc independent.
Effect of Carbohydrate Ingestion on the Glycemic Response of Type 1 Diabetic Adolescents During Exercise
Authors: Claudia Perrone, Orlando Laitano, Flávia Meyer
Journal: Diabetes Care (2005)

Ingestion of a drink containing sufficient carbohydrates can result in avoidance of exercise-induced hypoglycemia in type 1 diabetic individuals. In a previous study (1), we analyzed the effect of ingesting a drink with 6% carbohydrate (0.636 g/kg) on blood glucose concentration in type 1 diabetic adolescents during 60 min of moderate exercise and after 30 min of recovery. At the end of the trial, blood glucose concentration was reduced by 21 mg/dl.

Drink concentrations of >6% carbohydrate may help to prevent blood glucose reduction during exercise in type 1 diabetic subjects. However, the increased osmolality of high-carbohydrate drinks may cause gastrointestinal distress (2). This study aimed to determine whether carbohydrate solutions (8 and 10%) could prevent exercise blood glucose drops and to examine the gastrointestinal symptoms in type 1 diabetic adolescents.

Sixteen subjects (10 males and 6 females, age 16.1 ± 0.6 years, weight 62.8 ± 9.8 kg, height 168.3 ± 13.6 cm) volunteered to participate in the study and provided written informed consent. The mean duration of the condition was 7.3 ± 0.01 years, HbA1c was 6.8 ± 3.3%, and there were no chronic complications. Subjects were taking intermediate-acting or ultralong-acting insulin. The ethical committee of Hospital de Clinicas de Porto Alegre approved the study.

Both drinks were prepared by adding glucose and fructose to a solution with 4% sucrose and 2% …
Epidemiologic Research on the Etiology of Injuries at Work
Authors: M. A. Veazie, D. D. Landen, T. R. Bender, H. E. Amandus
Journal: Annual Review of Public Health (1994)

In recent decades, there has been remarkable growth in scientific research examining the multiple ways in which racism can adversely affect health. This interest has been driven in part by the striking persistence of racial/ethnic inequities in health and ...Read More
Internet to boost patient accrual in oncology trials? A multiinstitutional AERIO study
Authors: M.J. Rodrigues, S. Haberer, D. Dionysopoulos, J. Barrière, J. Wassermann, Y. Tazi, S. Rajpar, J. Giroux, F.-C. Bidard, Y. Loriot
Journal: Annals of Oncology (2011)
RECEPTORS FOR AGGREGATED IgG ON MOUSE LYMPHOCYTES
Authors: Clark L. Anderson, Howard M. Grey
Journal: The Journal of Experimental Medicine (1974)

An autoradiographic binding assay employing (125)I-labeled heat-aggregated mouse IgG2b myeloma protein (MOPC 141) was used to demonstrate receptors for IgG on 20-45% of Balb/c thymocytes and on 70-80% of splenocytes. Binding could also be shown with heat or BDB aggregates of another IgG2b (MOPC 195), with IgG1 and with human gamma-globulin, but not with aggregated chicken gamma-globulin, IgA, BSA, nor with aggregated Fab fragments of IgG2b. Optimum binding was obtained at 37 degrees C. Detection of binding was dependent upon aggregate size with complexes of more than 100 IgG molecules being optimal, aggregates of 6-25 detecting splenocytes but not thymocytes, and aggregates of less than 6 binding to a negligible extent. Comparison of grain counts on various cell types showed mastocytoma cells (P815) and macrophages averaging 40-50 grains/cell/day, allogeneically activated thymocytes 20-30, splenocytes 2-3, L5178 lymphoma cells 1, and positive thymocytes 0.6 grains/cell/day. Double labeling experiments for surface Ig, theta-antigen, and agg IgG receptor on mouse spleen cells indicated that a relatively high density of receptor was present on about 80% of B cells, 30% of T cells, and 60% of SIg(-), theta(-), null cells.
A Randomized, Double-Blind, Placebo-Controlled, Phase II Study Comparing the Tolerability and Efficacy of Ipilimumab Administered with or without Prophylactic Budesonide in Patients with Unresectable Stage III or IV Melanoma
Authors: Jeffrey Weber, John A. Thompson, Omid Hamid, David Minor, Asim Amin, Ilan Ron, Ruggero Ridolfi, Hazem Assi, Anthony Maraveyas, David Berman, Jonathan Siegel, Steven J. O'Day
Journal: Clinical Cancer Research (2009)

Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated with ipilimumab. A randomized, double-blind, placebo-controlled, multicenter, multinational phase II trial was conducted to determine whether prophylactic budesonide (Entocort EC), a nonabsorbed oral steroid, reduced the rate of grade >or=2 diarrhea in ipilimumab-treated patients with advanced melanoma.Previously treated and treatment-naïve patients (N = 115) with unresectable stage III or IV melanoma received open-label ipilimumab (10 mg/kg every 3 weeks for four doses) with daily blinded budesonide (group A) or placebo (group B) through week 16. The first scheduled tumor evaluation was at week 12; eligible patients received maintenance treatment starting at week 24. Diarrhea was assessed using Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Patients kept a diary describing their bowel habits.Budesonide did not affect the rate of grade >or=2 diarrhea, which occurred in 32.7% and 35.0% of patients in groups A and B, respectively. There were no bowel perforations or treatment-related deaths. Best overall response rates were 12.1% in group A and 15.8% in group B, with a median overall survival of 17.7 and 19.3 months, respectively. Within each group, the disease control rate was higher in patients with grade 3 to 4 irAEs than in patients with grade 0 to 2 irAEs, although many patients with grade 1 to 2 irAEs experienced clinical benefit. Novel patterns of response to ipilimumab were observed.Ipilimumab shows activity in advanced melanoma, with encouraging survival and manageable adverse events. Budesonide should not be used prophylactically for grade >or=2 diarrhea associated with ipilimumab therapy.
Molecular Pathways: Deregulation of Histone H3 Lysine 27 Methylation in Cancer—Different Paths, Same Destination
Authors: Teresa Ezponda, Jonathan D. Licht
Journal: Clinical Cancer Research (2014)

Methylation of lysine 27 on histone H3 (H3K27me), a modification associated with gene repression, plays a critical role in regulating the expression of genes that determine the balance between cell differentiation and proliferation. Alteration of the level of this histone modification has emerged as a recurrent theme in many types of cancer, demonstrating that either excess or lack of H3K27 methylation can have oncogenic effects. Cancer genome sequencing has revealed the genetic basis of H3K27me deregulation, including mutations of the components of the H3K27 methyltransferase complex PRC2 and accessory proteins, and deletions and inactivating mutations of the H3K27 demethylase UTX in a wide variety of neoplasms. More recently, mutations of lysine 27 on histone H3 itself were shown to prevent H3K27me in pediatric glioblastomas. Aberrant expression or mutations in proteins that recognize H3K27me3 also occur in cancer and may result in misinterpretation of this mark. In addition, due to the cross-talk between different epigenetic modifications, alterations of chromatin modifiers controlling H3K36me, or even mutations of this residue, can ultimately regulate H3K27me levels and distribution across the genome. The significance of mutations altering H3K27me is underscored by the fact that many tumors harboring such lesions often have a poor clinical outcome. New therapeutic approaches targeting aberrant H3K27 methylation include small molecules that block the action of mutant EZH2 in germinal center-derived lymphoma. Understanding the biologic consequences and gene expression pathways affected by aberrant H3K27 methylation may also lead to other new therapeutic strategies.
Phase I Trial and Pharmacokinetic Study of Lexatumumab in Pediatric Patients With Solid Tumors
Authors: Melinda S. Merchant, James I. Geller, Kristin Baird, Alexander J. Chou, Susana Galli, Ava Charles, Martha Amaoko, Eunice H. Rhee, Anita Price, Leonard H. Wexler, Paul A. Meyers, Brigitte C. Widemann, Maria Tsokos, Crystal L. Mackall
Journal: Journal of Clinical Oncology (2012)

Purpose Lexatumumab is an agonistic, fully human monoclonal antibody against tumor necrosis factor–related apoptosis-inducing ligand receptor 2 with preclinical evidence of activity in pediatric solid tumors. Patients and Methods This phase I dose-escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of lexatumumab at doses up to, but not exceeding, the adult maximum-tolerated dose (3, 5, 8, and 10 mg/kg), administered once every 2 weeks to patients age ≤ 21 years with recurrent or progressive solid tumors. Results Twenty-four patients received a total of 56 cycles of lexatumumab over all four planned dose levels. One patient had grade 2 pericarditis consistent with radiation recall, and one patient developed grade 3 pneumonia with hypoxia during the second cycle. Five patients experienced stable disease for three to 24 cycles. No patients experienced complete or partial response, but several showed evidence of antitumor activity, including one patient with recurrent progressive osteosarcoma who experienced resolution of clinical symptoms and positron emission tomography activity, ongoing more than 1 year off therapy. One patient with hepatoblastoma showed a dramatic biomarker response. Conclusion Pediatric patients tolerate 10 mg/kg of lexatumumab administered once every 14 days, the maximum-tolerated dose identified in adults. The drug seems to mediate some clinical activity in pediatric solid tumors and may work with radiation to enhance antitumor effects.
Regulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity in murine epidermis. Modulation of enzyme content and activation state by barrier requirements.
Authors: E Proksch, P M Elias, K R Feingold
Journal: Journal of Clinical Investigation (1990)

Epidermal cholesterol biosynthesis is regulated by barrier function. We quantitated the amount and activation state (phosphorylation-dephosphorylation) of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, in epidermis before and after barrier disruption. In murine epidermis we found high enzyme activity (1.75 +/- 0.02 nmol/min per mg protein). After acute barrier disruption, enzyme activity began to increase after 1.5 h, reaching a maximum increase by 2.5 h, and returned to normal by 15 h. Chronic barrier disruption increased total enzyme activity by 83%. In normal epidermis, measurement of HMG CoA reductase activity in microsomes isolated in NaF- vs. NaCl-containing buffers demonstrated that 46 +/- 2% of the enzyme was in the active form. After acute or chronic barrier disruption, a marked increase in the percentage of HMG CoA reductase in the active form was observed. Acute disruption increased enzyme activation state as early as 15 min, reaching a maximum after 2.5 h, with an increase still present at 15 h, indicating that changes in activation state had a close temporal relationship with barrier function. Increases in total HMG CoA reductase activity occurred only after profound barrier disruption, whereas changes in activation state occur with lesser degrees of barrier disruption. Artificial correction of barrier function prevented the increase in total HMG CoA reductase activity, and partially prevented the increase in enzyme activation. These results show that barrier requirements regulate epidermal cholesterol synthesis by modulating both the HMG CoA reductase amount and activation state.
p21-Activated Kinase Signaling Regulates Oxidant-Dependent NF-κB Activation by Flow
Authors: A. Wayne Orr, Cornelia Hahn, Brett R. Blackman, Martin Alexander Schwartz
Journal: Circulation Research (2008)

Disturbed blood flow induces inflammatory gene expression in endothelial cells, which promotes atherosclerosis. Flow stimulates the proinflammatory transcription factor nuclear factor (NF)-kappaB through integrin- and Rac-dependent production of reactive oxygen species (ROS). Previous work demonstrated that NF-kappaB activation by flow is matrix-specific, occurring in cells on fibronectin but not collagen. Activation of p21-activated kinase (PAK) followed the same matrix-dependent pattern. We now show that inhibiting PAK in cells on fibronectin blocked NF-kappaB activation by both laminar and oscillatory flow in vitro and at sites of disturbed flow in vivo. Constitutively active PAK rescued flow-induced NF-kappaB activation in cells on collagen. Surprisingly, PAK was not required for flow-induced ROS production. Instead, PAK modulated the ability of ROS to activate the NF-kappaB pathway. These data demonstrate that PAK controls NF-kappaB activation by modulating the sensitivity of cells to ROS.
II. POLIOMYELITIC VIRUS IN URBAN SEWAGE
Authors: John R. Paul, James D. Trask, Sven Gard
Journal: The Journal of Experimental Medicine (1940)

In two out of three large urban epidemics of poliomyelitis the virus of this disease has been detected in samples of sewage. From one of the sites it was found repeatedly. Both positive sites were located in the vicinity of isolation hospitals, and we believe that the findings indicate that this virus can be transported, for short distances at least, through the medium of flowing sewage.
Evolutionary Dynamics of the Human NADPH Oxidase Genes CYBB, CYBA, NCF2, and NCF4: Functional Implications
Authors: Eduardo Tarazona-Santos, Moara Machado, Wagner C.S. Magalhães, Renee Chen, Fernanda Lyon, Laurie Burdett, Andrew Crenshaw, Cristina Fabbri, Latife Pereira, Laelia Pinto, Rodrigo A.F. Redondo, Ben Sestanovich, Meredith Yeager, Stephen J. Chanock
Journal: Molecular Biology and Evolution (2013)

The phagocyte NADPH oxidase catalyzes the reduction of O2 to reactive oxygen species with microbicidal activity. It is composed of two membrane-spanning subunits, gp91-phox and p22-phox (encoded by CYBB and CYBA, respectively), and three cytoplasmic subunits, p40-phox, p47-phox, and p67-phox (encoded by NCF4, NCF1, and NCF2, respectively). Mutations in any of these genes can result in chronic granulomatous disease, a primary immunodeficiency characterized by recurrent infections. Using evolutionary mapping, we determined that episodes of adaptive natural selection have shaped the extracellular portion of gp91-phox during the evolution of mammals, which suggests that this region may have a function in host-pathogen interactions. On the basis of a resequencing analysis of approximately 35 kb of CYBB, CYBA, NCF2, and NCF4 in 102 ethnically diverse individuals (24 of African ancestry, 31 of European ancestry, 24 of Asian/Oceanians, and 23 US Hispanics), we show that the pattern of CYBA diversity is compatible with balancing natural selection, perhaps mediated by catalase-positive pathogens. NCF2 in Asian populations shows a pattern of diversity characterized by a differentiated haplotype structure. Our study provides insight into the role of pathogen-driven natural selection in an innate immune pathway and sheds light on the role of CYBA in endothelial, nonphagocytic NADPH oxidases, which are relevant in the pathogenesis of cardiovascular and other complex diseases.