tbuckley/cabot-search huggingface dataset:
Ebola Virus Disease and Children
Authors: Georgina Peacock, Timothy M. Uyeki, Sonja A. Rasmussen
Journal: JAMA Pediatrics (2014)

The largest outbreak of Ebola virus disease (EVD) in history is occurring in West Africa. On August 8, 2014, the World Health Organization (WHO) declared this outbreak to be a Public Health Emergency of International Concern.1 As of October 8, 2014, 8399 EVD cases (including 416 in health care personnel) with 4033 deaths were reported, although reported cases are likely a substantial underestimate of the outbreak magnitude.2 Most EVD cases have been reported in Guinea, Liberia, and Sierra Leone, with fewer cases in Nigeria and a single case in Senegal. Although the suspected index case for this outbreak is believed to be a 2-year-old child who died in Guinea in December 2013, limited information is available on the impact of this outbreak on children.3 Cases of EVD were also identified in the Democratic Republic of the Congo, but analyses of viruses suggest that the Democratic Republic of the Congo outbreak is not linked to the wider epidemic. As of October 15, 2014, 3 EVD cases, including 2 health care personnel, had been identified in the United States and 5 EVD cases, including 4 health care personnel, were identified in West Africa and medically evacuated to the United States for further care. This situation is rapidly evolving, and new information will be posted to the Centers for Disease Control and Prevention (CDC) (http://www.cdc.gov/vhf/ebola/index.html) and WHO (http://www.who.int/mediacentre/factsheets/fs103/en/) websites as it becomes available. Our report is intended to complement information on the CDC webpages, with a focus on what pediatric health care professionals need to know.
Activation of the Platelet-Derived Growth Factor-Receptor Enhances Survival of Murine Bone Endothelial Cells
Authors: Robert R. Langley, Dominic Fan, Rachel Z. Tsan, Robert Rebhun, Junqin He, Sun-Jin Kim, Isaiah J. Fidler
Journal: Cancer Research (2004)

Abstract The activation of the microvascular endothelial cell platelet-derived growth factor (PDGF) receptor (PDGF-R) by PDGF has been implicated in neoplastic angiogenesis. Here, we established cultures of murine bone microvascular endothelial cells and examined their response to stimulation with PDGF BB ligand and to blockade of PDGF-R signaling with the tyrosine kinase inhibitor STI571 (Gleevec). The addition of STI571 to cultures of bone endothelial cells blocked PDGF BB-induced phosphorylation in a dose-dependent manner and completely abrogated the activation of downstream targets Akt and ERK1/2. Coadministration of STI571 and Taxol also induced the activation of procaspase-3 and significant apoptosis. These data suggest that phosphorylation of PDGF-R stimulates survival pathways in bone endothelial cells and that by selectively inhibiting PDGF-R signaling with STI571, the cells are rendered sensitive to Taxol treatment. The therapeutic combination of STI571 and Taxol may be a powerful tool for targeting tumor-associated endothelial cells in the skeletal compartment.
Genome-wide analysis of target genes regulated by HoxB4 in hematopoietic stem and progenitor cells developing from embryonic stem cells
Authors: Motohiko Oshima, Mitsuhiro Endoh, Takaho A. Endo, Tetsuro Toyoda, Yaeko Nakajima-Takagi, Fumihiro Sugiyama, Haruhiko Koseki, Michael Kyba, Atsushi Iwama, Mitsujiro Osawa
Journal: Blood (2011)
Gene Set Enrichment Analysis Unveils the Mechanism for the Phosphodiesterase 4B Control of Glucocorticoid Response in B-cell Lymphoma
Authors: Sang-Woo Kim, Deepak Rai, Ricardo C.T. Aguiar
Journal: Clinical Cancer Research (2011)

Resistance to glucocorticoid (GC) is a significant problem in the clinical management of lymphoid malignancies. Addressing this issue via a mechanistic understanding of relevant signaling pathways is more likely to yield positive outcomes.We used gene set enrichment analysis (GSEA), multiple genetic models of gain and loss of function in B-cell lymphoma cell lines, in vitro and in vivo, and primary patient samples to characterize a novel relationship between the cyclic AMP/phosphodiesterase 4B (cAMP/PDE4B), AKT/mTOR activities, and GC responses.Starting from the GSEA, we found that overexpression of the PDE4B in diffuse large B-cell lymphoma (DLBCL) impinge on the same genes/pathways that are abnormally active in GC-resistant tumors. We used genetically modified cell lines to show that PDE4B modulates cAMP inhibitory activities toward the AKT/mTOR pathway and defines GC resistance in DLBCL. In agreement with these data, pharmacologic inhibition of PDE4 in a xenograft model of human lymphoma unleashed cAMP effects, inhibited AKT, and restored GC sensitivity. Finally, we used primary DLBCL samples to confirm the clinical relevance and biomarker potential of AKT/mTOR regulation by PDE4B.Together, these data mechanistically elucidated how cAMP modulates GC responses in lymphocytes, defined AKT as the principal transducer of the growth inhibitory effects of cAMP in B cells, and allowed the formulation of genomics-guided clinical trials that test the ability of PDE4 inhibitors to restore GC sensitivity and improve the outcome of patients with B-cell malignancies.
Anemia and Diabetes in the Absence of Nephropathy
Authors: Kathrine J. Craig, John D. Williams, Stephen G. Riley, Hilary Smith, David R. Owens, Debbie Worthing, Ivor Cavill, Aled O. Phillips
Journal: Diabetes Care (2005)

OBJECTIVE—Patients with diabetes commonly have a greater degree of anemia for their level of renal impairment than those presenting with other causes of renal failure. To clarify the contribution and differing roles of diabetes and nephropathy in the development of anemia in diabetic patients, we examined the hematologic and hematinic parameters of diabetic patients without nephropathy. RESEARCH DESIGN AND METHODS—The study group was comprised of 62 patients with type 2 diabetes who had been followed for a median of 7 years. For the study, these patients had additional samples taken during their annual routine blood testing for the measurement of extra parameters, including serum ferritin, serum erythropoietin (Epo) levels, and the percentage of reticulocytes. These measurements were combined with the routine parameters Hb, hematocrit, HbA1c, and glomerular filtration rate. RESULTS—In all, 8 of the 45 male patients (17.8%) and 2 of the 17 female patients (11.8%) were classified as anemic (Hb &amp;lt;13g/dl and &amp;lt;11.5g/dl, respectively). Although only a small number of the patients had anemia as defined by normal values, a retrospective analysis of individual patients over time revealed a sustained though small decrease in Hb from initial presentation. A statistically significant difference in Epo levels (P = 0.016 by Kruskal-Wallis test) was observed from the group with the lowest (Hb ≤11.5) to that with the highest (Hb ≥14.5) Hb values, with a median Epo value of 37 (interquartile range 24–42) vs. 13 (9–15) IU/l, respectively. In contrast, there was no evidence of an increased reticulocyte response to higher levels of Epo (r = 0.134 [Pearsons], P = 0.36). Reticulocyte counts ranged from 44 (38–57) to 76.5 (56–83) in the lowest and highest Hb groups, respectively. CONCLUSIONS—Although only a small number of subjects in the group were overtly anemic, all subjects had an ongoing, small but significant decrease in Hb since presentation. This study of diabetic patients without nephropathy shows an expected increase in Epo production in response to lowering levels of Hb but without the expected reticulocyte response.
Effects of different transferrin forms on transferrin receptor expression, iron uptake, and cellular proliferation of human leukemic HL60 cells. Mechanisms responsible for the specific cytotoxicity of transferrin-gallium.
Authors: C R Chitambar, P A Seligman
Journal: Journal of Clinical Investigation (1986)

We have previously shown that human leukemic cells proliferate normally in serum-free media containing various transferrin forms, but the addition of transferrin-gallium leads to inhibition of cellular proliferation. Because gallium has therapeutic potential, the effects of transferrin-gallium on leukemic cell proliferation, transferrin receptor expression, and cellular iron utilization were studied. The cytotoxicity of gallium is considerably enhanced by its binding to transferrin and cytotoxicity can be reversed by transferrin-iron but not by other transferrin forms. Exposure to transferrin-gallium leads to a marked increase in cell surface transferrin binding sites, but despite this, cellular 59Fe incorporation is inappropriately low. Although shunting of transferrin-gallium to another cellular compartment has not been ruled out, other studies suggest that transferrin-gallium impairs intracellular release of 59Fe from transferrin by interfering with processes responsible for intracellular acidification. These studies, taken together, demonstrate that inhibition of cellular iron incorporation by transferrin-gallium is a prerequisite for inhibition of cellular proliferation.
Breast-feeding, aeroallergen sensitization, and environmental exposures during infancy are determinants of childhood allergic rhinitis
Authors: Christopher D. Codispoti, Linda Levin, Grace K. LeMasters, Patrick Ryan, Tiina Reponen, Manuel Villareal, Jeff Burkle, Sherry Stanforth, James E. Lockey, Gurjit K. Khurana Hershey, David I. Bernstein
Journal: Journal of Allergy and Clinical Immunology (2010)
Tauroursodeoxycholic acid exerts anticholestatic effects by a cooperative cPKC -/PKA-dependent mechanism in rat liver
Authors: R Wimmer, S Hohenester, T Pusl, G U Denk, C Rust, U Beuers
Journal: Gut (2008)

Ursodeoxycholic acid (UDCA) exerts anticholestatic effects in part by protein kinase C (PKC)-dependent mechanisms. Its taurine conjugate, TUDCA, is a cPKC alpha agonist. We tested whether protein kinase A (PKA) might contribute to the anticholestatic action of TUDCA via cooperative cPKC alpha-/PKA-dependent mechanisms in taurolithocholic acid (TLCA)-induced cholestasis.In perfused rat liver, bile flow was determined gravimetrically, organic anion secretion spectrophotometrically, lactate dehydrogenase (LDH) release enzymatically, cAMP response-element binding protein (CREB) phosphorylation by immunoblotting, and cAMP by immunoassay. PKC/PKA inhibitors were tested radiochemically. In vitro phosphorylation of the conjugate export pump, Mrp2/Abcc2, was studied in rat hepatocytes and human Hep-G2 hepatoma cells.In livers treated with TLCA (10 micromol/l)+TUDCA (25 micromol/l), combined inhibition of cPKC by the cPKC-selective inhibitor Gö6976 (100 nmol/l) or the non-selective PKC inhibitor staurosporine (10 nmol/l) and of PKA by H89 (100 nmol/l) reduced bile flow by 36% (p<0.05) and 48% (p<0.01), and secretion of the Mrp2/Abcc2 substrate, 2,4-dinitrophenyl-S-glutathione, by 31% (p<0.05) and 41% (p<0.01), respectively; bile flow was unaffected in control livers or livers treated with TUDCA only or TLCA+taurocholic acid. Inhibition of cPKC or PKA alone did not affect the anticholestatic action of TUDCA. Hepatic cAMP levels and CREB phosphorylation as readout of PKA activity were unaffected by the bile acids tested, suggesting a permissive effect of PKA for the anticholestatic action of TUDCA. Rat and human hepatocellular Mrp2 were phosphorylated by phorbol ester pretreatment and recombinant cPKC alpha, nPKC epsilon, and PKA, respectively, in a staurosporine-sensitive manner.UDCA conjugates exert their anticholestatic action in bile acid-induced cholestasis in part via cooperative post-translational cPKC alpha-/PKA-dependent mechanisms. Hepatocellular Mrp2 may be one target of bile acid-induced kinase activation.
Induction of Apoptosis Using Inhibitors of Lysophosphatidic Acid Acyltransferase-β and Anti-CD20 Monoclonal Antibodies for Treatment of Human Non-Hodgkin's Lymphomas
Authors: John M. Pagel, Christian Laugen, Lynn Bonham, Robert C. Hackman, David M. Hockenbery, Rama Bhatt, David Hollenback, Heather Carew, Jack W. Singer, Oliver W. Press
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Lysophosphatidic acid acyltransferase-β (LPAAT-β) is a transmembrane enzyme critical for the biosynthesis of phosphoglycerides whose product, phosphatidic acid, plays a key role in raf and AKT/mTor-mediated signal transduction. Experimental Design: LPAAT-β may be a novel target for anticancer therapy, and, thus, we examined the effects of a series of inhibitors of LPAAT-β on multiple human non–Hodgkin's lymphoma cell lines in vitro and in vivo. Results: We showed that five LPAAT-β inhibitors at doses of 500 nmol/L routinely inhibited growth in a panel of human lymphoma cell lines in vitro by &amp;gt;90%, as measured by [3H]thymidine incorporation. Apoptotic effects of the LPAAT-β inhibitors were evaluated either alone or in combination with the anti-CD20 antibody, Rituximab. The LPAAT-β inhibitors induced caspase-mediated apoptosis at 50 to 100 nmol/L in up to 90% of non–Hodgkin's lymphoma cells. The combination of Rituximab and an LPAAT-β inhibitor resulted in a 2-fold increase in apoptosis compared with either agent alone. To assess the combination of Rituximab and a LPAAT-β inhibitor in vivo, groups of athymic mice bearing s.c. human Ramos lymphoma xenografts were treated with the LPAAT-β inhibitor CT-32228 i.p. (75 mg/kg) daily for 5 d/wk × 4 weeks (total 20 doses), Rituximab i.p. (10 mg/kg) weekly × 4 weeks (4 doses total), or CT-32228 plus Rituximab combined. Treatment with either CT-32228 or Rituximab alone showed an approximate 50% xenograft growth delay; however, complete responses were only observed when the two agents were delivered together. Conclusions: These data suggest that Rituximab, combined with a LPAAT-β inhibitor, may provide enhanced therapeutic effects through apoptotic mechanisms.
Myocardial Performance in Hemorrhagic Shock in the Dog and Primate
Authors: FRANCIS L. ABEL, DAVID P. KESSLER
Journal: Circulation Research (1973)

Myocardial performance was investigated in nine dogs and six monkeys during experimental hemorrhagic shock under conditions of constant afterload. Left ventricular function curves were obtained by opening an aorta to left atrial bypass, and simultaneous recordings of stroke volume, peak stroke power, maximal dP/dt, maximal dF/dt, heart rate, atrial pressure and end-diastolic pressure were made. Total plasma catecholamine content was also measured in the monkeys during the control period and at death. The dogs showed a marked increase in performance, in contrast to the control group, 0-2 hours after reinfusion. Performance then deteriorated significantly by 2-4 hours, although it was still comparable to control levels. However, higher atrial and end-diastolic pressures were obtained, and in most cases cardiac failure developed soon thereafter. Two additional dogs were subjected to all stresses except the hypotension for 10 hours without evidence of deterioration. The monkeys did not withstand the surgical procedure as well as the dogs did and survived a maximum of 136 minutes after reinfusion. Catecholamine levels decreased in five of the six monkeys but not below normal levels, which indicates that failure was not due to depletion of myocardial stores. The data are interpreted as direct evidence for a factor(s) seriously depressing myocardial performance during the postinfusion period of experimental hemorrhagic shock in the dog and the monkey despite the high levels of performance in the early postinfusion period and the maintenance of coronary driving pressure and arterial oxygen content.
Natural course of sleep disordered breathing after acute myocardial infarction
Authors: Charalampos Mermigkis, Izolde Bouloukaki, Sophia E. Schiza
Journal: European Respiratory Journal (2013)

To the Editor: 

In a recent issue of the European Respiratory Journal , Buchner et al. [1] reported an alleviation of sleep apnoea in 40 patients with acute myocardial infarction (AMI) 12 weeks after the event, associated with an improvement of ≥5% in the ejection fraction (EF). Moderate to severe sleep apnoea was observed in 55% of the patients. At the second evaluation the respiratory events were reduced significantly more in the improved EF group. The authors' novel observation was that the decrease in the apnoea–hypopnoea index (AHI) was the result of a reduction in obstructive, but not central respiratory events.

Our own study of the time course of sleep apnoea after a first AMI was published several months earlier in the Journal of Clinical Sleep Medicine [2], although it was not cited by Buchner et al. [1]. The study included 52 patients with first-ever acute coronary syndrome (ACS) who underwent polysomnography (PSG) on the third day after the acute cardiac event and were re-evaluated with PSG 1 …
An articular index for the assessment of osteoarthritis.
Authors: D V Doyle, P A Dieppe, J Scott, E C Huskisson
Journal: Annals of the Rheumatic Diseases (1981)

An articular index was devised for the sequential assessment of patients with osteo- arthritis (OA).Forty-eight joint units, chosen to reflect the characteristic pattern of the disease, were scored for tenderness on pressure or movement on a 4-point scale.Four observers examined patients to assess interand intraobserver error.The index was highly reproducible both within and between observers; intraobserver error was, however, significantly smaller.In a double-blind, cross-over trial the index was sufficiently sensitive to detect a statistically significant difference between the responses of patients with OA to an anti-inflammatory agent and to a simple analgesic.It is likely to be a useful addition to current methods of measurement in osteoarthritis.
Treatment of Single Brain Metastasis with Resection, Intracavity Carmustine Polymer Wafers, and Radiation Therapy Is Safe and Provides Excellent Local Control
Authors: Matthew G. Ewend, Steven Brem, Mark Gilbert, Robert Goodkin, Paul L. Penar, Mahesh Varia, Sharon Cush, Lisa A. Carey
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To define the safety and efficacy of carmustine polymer wafers when added to a regimen of surgery and external beam radiotherapy for treatment of a single brain metastasis. Experimental Design: Adult patients underwent craniotomy for a single brain metastasis, and carmustine polymer wafers were placed in the tumor resection cavity. Patients then received whole-brain radiotherapy and were followed for patterns of recurrence in the central nervous system, toxicity, and survival. Results: We enrolled 25 patients with solitary brain metastases from lung (13 patients), melanoma (4 patients), breast (3 patients), and renal carcinoma (3 patients). Two patients had severe adverse events thought to be related to wafer placement, one with seizures alone, and one with seizures and subsequent respiratory compromise. Both responded to medical therapy. There were no wound infections. The local recurrence rate was surprisingly low (0%). Four patients (16%) relapsed elsewhere in the brain, and two patients (8%) relapsed in the spinal cord. Median survival was 33 weeks; 33% of patients survived 1 year, and 25% survived 2 years. Conclusions: The addition of local chemotherapy delivered via carmustine polymer wafers to a regimen of surgical resection and external beam radiotherapy was well tolerated by patients undergoing surgery for a single brain metastasis. There were no local recurrences, suggesting that this treatment further reduced the risk of local relapse.
High-dose chemotherapy and autologous stem cell transplantation in peripheral T-cell lymphoma: the GEL-TAMO experience
Authors: J. Rodríguez, M.D. Caballero, A. Gutiérrez, J. Marín, J.J. Lahuerta, A. Sureda, E. Carreras, A. León, R. Arranz, A. Fernández de Sevilla, J. Zuazu, J. García-Laraña, J. Rifon, R. Varela, M. Gandarillas, J. SanMiguel, E. Conde
Journal: Annals of Oncology (2003)
Evolution of the large-subunit ribosomal RNA binding site for protein L23/25
Authors: A. Chenuil, M. Solignac, M. Bernard
Journal: Molecular Biology and Evolution (1997)

The region of the large-subunit rRNA encompassing the D7 divergent domain is organized within eukaryotes in a patchwork of short conservative secondary-structure features interspersed with more rapidly evolving sequences. It contains the attachment site of protein L25 (E. coli L23), which binds rRNA in the first stages of ribosome assembly, suggesting a crucial importance of this region in ribosome elaboration and functioning. A better understanding of its roles requires a good knowledge of its mode of structural variation during the course of evolution. With this aim, we sequenced the D7 region for 24 new invertebrate species belonging to annelids, molluscs, arthropods, and eight other deep-branching invertebrate phyla. Their comparison allowed us to propose refinements in previous eukaryotic folding models. A detailed analysis of the pattern of variation at each position both within the D7 region and along the L23/25 sequence by reference to previous heterologous binding experiments gives new insight into the rRNA-protein contacts. We identified in the D7 region and L23/25, respectively, six and five positions presenting a pattern of variation compatible with experimental results, three of which show coincident variations which support their possible involvement in the rRNA-L23/25 binding.
THE LIPIDS OF SERUM AND LIVER IN PATIENTS WITH HEPATIC DISEASES 1
Authors: Evelyn B. Man, Bernard L. Kartin, Stanley H. Durlacher, John P. Peters
Journal: Journal of Clinical Investigation (1945)

The investigations of dietary fatty livers have thrown into prominent relief the function of the liver in the intermediary metabolism of lipids.The discovery that these disorders may be reme- died or prevented by lipotropic agents may have important therapeutic implications since there is some evidence that the chemical and anatomical disturbances of the liver produced by some dis- eases and poisons resemble those found in dietary livers and that they may be amenable to the action of these lipotropic agents (1 to 3).These were among the reasons that led to an examination of the serum lipids in patients with diseases of the liver and pancreas and obstruction of the biliary
The Marital Relationship and Psychosocial Adaptation and Glycemic Control of Individuals With Diabetes
Authors: Paula M. Trief, Christine L. Himes, Rebecca Orendorff, Ruth S. Weinstock
Journal: Diabetes Care (2001)

To explore the relationship between marital relationship domains (i.e., intimacy and adjustment) and glycemic control and psychosocial adaptation to diabetes.A total of 78 insulin-treated adults with both type 1 and type 2 diabetes were assessed on a single occasion. They completed two marital quality measures (Spanier Dyadic Adjustment Scale and Personal Assessment of Intimacy in Relationships Scale) and four quality-of-life measures (Diabetes Quality of Life Scale, Medical Outcomes Study Health Survey, Problem Areas in Diabetes Scale, and Positive and Negative Affect Scale). Glycemic control was assessed by HbA(1c). Demographic data (age, sex, type and duration of diabetes, years married, other medical conditions, family history, disability, and years of education) were gathered from the chart and questionnaires.Concerning psychosocial adaptation, both of the marital quality measures were predictors of aspects of adaptation. Better marital satisfaction was related to higher levels of diabetes-related satisfaction and less impact, as well as less diabetes-related distress and better general quality of life. Higher levels of marital intimacy were related to better diabetes-specific and general quality of life. Concerning glycemic control, there was a nonsignificant trend for marital adjustment scores to relate to HbA(1c) (P = 0.0568).For insulin-treated adults with diabetes, quality of marriage is associated with adaptation to diabetes and other aspects of health-related quality of life. The suggestive finding that marital adjustment may relate to glycemic control warrants further study. Future work should also explore the impact of couples-focused interventions on adaptation, adherence, and glycemic control.