tbuckley/cabot-search huggingface dataset:
Abstract 1986: Tumor suppressor PDCD4 inhibits NFκB dependent transcription in human glioblastoma cells by direct interaction with p65.
Authors: Soon-Kyung Hwang, Matthew R. Young, Nancy H. Colburn
Journal: Cancer Research (2013)

Abstract PDCD4 was first described as a protein induced by apoptotic stimuli that acts as a tumor suppressor. PDCD4 plays an important role in regulating translation and transcription. Our previous research showed that overexpression of PDCD4 leads to decreased anchorage independent growth in glioblastoma-derived cell lines as well as decreased tumor growth in a glioblastoma xenograft model. Moreover, PDCD4 positively influences tumor necrosis factor-induced activation of the transcription factor NF-κB in inflammatory cells. However, the effect of PDCD4 on NF-κB transcriptional activity in cancer cells is still unknown. NF-κB acts as an oncogenic driver in many cancer sites. We studied the effect of PDCD4 on NF-κB-dependent transcriptional activity in malignant human glioblastoma cell lines by stably overexpressing PDCD4 in GBM U251 and LN229 cells. Stable Pdcd4 expression inhibits NF-κB transcriptional activation measured by a luciferase reporter in U251 and LN229 cells. The molecular mechanism by which PDCD4 inhibits NF-κB transcriptional activation does not involve inhibited expression of NF-κB p65 or p50 proteins. PDCD4 overexpression does not inhibit pathways upstream of NF-κB including the activation of IKKalpha and IKKbeta kinases. In addition, PDCD4 does not inhibit phosphorylation or degradation of IκBα, events needed for nuclear transport of p65 and p50. Overexpression of PDCD4 does, however, inhibit translocation of p65 but not p50 to the nucleus. Pdcd4 protein interacts directly with p65 protein as shown by co-immunoprecipitation and confocal imaging. These results suggest that PDCD4 can significantly inhibit NF-κB activity in glioblastoma cells by a mechanism that involves direct protein-protein interaction rather than the expected mRNA-selective translational inhibition. These findings may provide novel opportunities for NF-κB targeted interventions to prevent or treat cancer. Citation Format: Soon-Kyung Hwang, Matthew R. Young, Nancy H. Colburn. Tumor suppressor PDCD4 inhibits NFκB dependent transcription in human glioblastoma cells by direct interaction with p65. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1986. doi:10.1158/1538-7445.AM2013-1986
Congenital Absence of the Gall Bladder with Cystic Dilatation of the Common Bile Duct
Authors: H. F. Rheinlander, Oliver L. Bowens
Journal: New England Journal of Medicine (1957)

THE present report concerns a patient who was successfully treated for cystic dilatation of the common bile duct associated with congenital absence of the gall bladder. Both these anomalies are rare, and a search of the literature reveals no report describing their coexistence. That their association may be confusing is borne out by the fact that two previous attempts at biliary-tract exploration were unsuccessful in arriving at a diagnosis or alleviating the patient's symptoms. In the present case, operative cholangiography delineated the malformation, which was treated by the performance of a Roux-en-Y choledochojejunostomy.Case ReportC. C. (N.E.C.H. 88–149), a . . .
Toll-like receptor 2 stimulation induces intimal hyperplasia and atherosclerotic lesion development
Authors: A SCHONEVELD, M OUDENIJHUIS, B VANMIDDELAAR, J LAMAN, D DEKLEIJN, G PASTERKAMP
Journal: Cardiovascular Research (2005)

Background: Toll like receptors (Tlr) are essential in activation of the innate immune system. We recently described that peptidoglycan, an exogenous Tlr2 specific ligand, is present in human atherosclerotic plaques and associated with histological markers for plaque vulnerability. Also, endogenous Tlr2 ligands can be expressed in atherosclerotic tissues. Here, we determined whether Tlr2 stimulation promotes pro-inflammatory cytokine/chemokine production in vitro and augments neointima formation and development of atherosclerotic plaques in vivo.
Diagnostic approach to anaphylaxis by carrot, related vegetables and horsetail (<i>Equisetum arvense</i>) in a homemaker
Authors: M. P. Agustìn‐Ubide, C. Martinez‐Cócera, A. Alonso‐Llamazares, T. Robledo, M. Lombardero, J. Dominguez, M. A. Carballo
Journal: Allergy (2004)
Effect of an Anti-Histamine in Rheumatoid Arthritis
Authors: D. C. Wilson
Journal: Annals of the Rheumatic Diseases (1953)

<h3>Abstract</h3> Mutant <i>KRAS</i> (KM) is the most common oncogene in lung cancer (LC). KM regulates several metabolic networks, but their role in tumorigenesis is still not sufficiently characterized to be exploited in cancer therapy. To identify metabolic networks specifically deregulated in KMLC, we characterized the lipidome of genetically engineered LC mice, cell lines, patient derived xenografts and primary human samples. We also determined that KMLC, but not EGFR-mutant (EGFR-MUT) LC, is enriched in triacylglycerides (TAG) and phosphatidylcholines (PC). We also found that KM upregulates fatty acid synthase (FASN), a rate-limiting enzyme in fatty acid (FA) synthesis promoting the synthesis of palmitate and PC. We determined that FASN is specifically required for the viability of KMLC, but not of LC harboring EGFR-MUT or wild type KRAS. Functional experiments revealed that FASN inhibition leads to ferroptosis, a reactive oxygen species (ROS)-and iron-dependent cell death. Consistently, lipidomic analysis demonstrated that FASN inhibition in KMLC leads to accumulation of PC with polyunsaturated FA (PUFA) chains, which are the substrate of ferroptosis. Integrating lipidomic, transcriptome and functional analyses, we demonstrated that FASN provides saturated (SFA) and monounsaturated FA (MUFA) that feed the Lands cycle, the main process remodeling oxidized phospholipids (PL), such as PC. Accordingly, either inhibition of FASN or suppression of the Lands cycle enzymes PLA2 and LPCAT3, promotes the intracellular accumulation of lipid peroxides and ferroptosis in KMLC both <i>in vitro</i> and <i>in vivo</i>. Our work supports a model whereby the high oxidative stress caused by KM dictates a dependency on newly synthesized FA to repair oxidated phospholipids, establishing a targetable vulnerability. These results connect KM oncogenic signaling, FASN induction and ferroptosis, indicating that FASN inhibitors already in clinical trial in KMLC patients (NCT03808558) may be rapidly deployed as therapy for KMLC.
High Rate of Tuberculin Conversion in Indochinese Refugees
Authors: Dale L. Morse
Journal: JAMA (1982)

From January 1979 through December 1980, a total of 664 Indochinese refugees were screened for tuberculosis in Monroe County, New York; 307 (46%) had positive 5-tuberculin unit PPD Mantoux tests. When 217 refugees with initially negative tests were retested at 60 days, 94 (43%) had converted from a negative to a positive test. Although none of the converters had evidence of active tuberculosis disease, 90 (96%) were given isoniazid preventive therapy. This conversion phenomenon has continued over time, discounting an effect of local, national, or international policy changes. The conversions do not seem to be a function of antigen, tester, or reader; criteria for testing, retesting, or reading; home country, camp country, or length of time in camp; or history of prior BCG vaccination, tuberculosis, or immunization exposure, current illness, or testing intervals since arrival in the United States and subsequent testing. Further studies to evaluate boosting or anergy are in progress to assess this potential public health problem.
Abstract 4921: Endothelial-targeted Expression of a Conditional Fas-fKBP Chimera in Transgenic Mice Establishes the Role of Lung Microvascular Apoptosis in Pulmonary Hypertension
Authors: Jin-Yi Jiang, Paul Jurasz, David W Courtman, Yupu Deng, Anli Yang, Qiuwang Zhang, Kursad Turksen, Tammy Sinclair, Duncan J Stewart
Journal: Circulation (2009)

Introduction: Pulmonary arterial hypertension (PAH) is a lethal disorder characterized by pulmonary arteriolar remodeling and obliteration. Although its pathogenesis is still unclear, endothelial cell (EC) apoptosis has been suggested to be an initiating event in PAH, possibly leading directly to the degeneration of fragile precapillary arterioles. This study was to create a transgenic model of tritrable EC apoptosis to test the hypothesis that this is sufficient to induce the PAH phenotype. Methods: The Fas-Induced Apoptosis (FIA) construct contains the Fas cytoplasmic death domain fused with 2 copies of the FK506-binding peptide (FKBP) domain. This construct was targeted to ECs (i.e. EFIA) under the control of the Tie2 promoter and apoptosis was induced by a small molecule dimerizing agent, AP20187, which binds tightly to the FKBP domain. After in vitro validation of its activity, the EFIA gene construct was microinjected into fertilized oocytes in CD1 mice. Apoptosis was assessed by TUNEL staining and right ventricular systolic pressure (RVSP) and hypertrophy (RV/LV+septal weight) were determined with and without i.p. injection of AP20187. Results: EFIA transgenic mice appeared normal, however, administration of the AP20187 at 10 mg/kg/day for 2 weeks resulted in an increase in RVSP, which was greater in homozygous vs. heterozygous EFIA mice (37 ± 7 and 31 ± 7 mm Hg, respectively) compared WT mice either with or without AP20187 (26 ± 2 and 23 ± 2, respectively; p = 0.02). As well, there was a significant increase in right ventricular remodeling in homozygous EFIA mice treated with AP20187 compared to WT mice (RV/LV+ septal wt: 0.366 ±0.132 vs. 0.244 ± 0.048, respectively). AP20187 treatment also induced apoptosis in the peripheral lung (0.22 ± 0.05%) as well as in the kidney (9 ± 2%), which was significantly correlated with increases in RVSP. Of noted, increased lung cell proliferation, as evidenced by PCNA staining, was seen only in AP20187-treated EFIA mice. Conclusions: These results provide the first evidence that EC apoptosis is sufficient to produce PAH. This was characterized in EFIA mice by both increased peripheral lung apoptosis and reactive cellular proliferation, thus representing a new tool to further explore the pathogenesis of the lethal disease.
This Day 50 Years Ago
Authors: Franz H. Messerli
Journal: New England Journal of Medicine (1995)

The headlines of April 13, 1945, stunned the nation and the world. Franklin D. Roosevelt, 32nd president of the United States, had died in Warm Springs, Georgia, the day before. Presumably, he had been in excellent health, there was no indication of imminent danger, and as Admiral Ross McIntire, the president's personal physician, asserted, the cerebral hemorrhage “came out of the clear sky” (Figure 1).1 Steve Early, press secretary for the White House, stated officially that “the President was given a thorough examination by seven or eight physicians, including some of the most eminent in the country, and was pronounced . . .
Dynamic Lymphoscintigraphy to Identify the Sentinel and Satellite Nodes
Authors: ANDREW TAYLOR, DOUGLAS MURRAY, STEVE HERDA, JOHN VANSANT, NAOMI ALAZRAKI
Journal: Clinical Nuclear Medicine (1996)

Lymphoscintigraphy is increasingly used to identify the first draining node (sentinel node) in patients with malignant melanoma or breast cancer. If the sentinel node is tumor free then the remainder of the nodes in that specific nodal bed are likely to be free of metastases. Localization and biopsy of the sentinel node with an intraoperative surgical probe may obviate more radical lymph node dissection. Lymphoscintigraphy is conventionally performed by injecting the radioactive tracer in the four quadrants around the primary tumor and imaging the appropriate nodal beds approximately 30 minutes later. The visualized node nearest the tumor usually is assumed to represent the sentinel node. To test this assumption, a dynamic acquisition was obtained in 16 patients with malignant melanoma to determine if the node nearest the tumor was actually the first draining node. In one of 16 patients, the radioactive tracer injected around a thigh melanoma drained first to an inguinal node and then drained inferiorly to a second inguinal node located closer to the tumor. The distinction between the sentinel and satellite (secondary draining nodes) may have important clinical implications regarding the number of nodes that require surgical excision. In summary, static images do not define the pattern of lymph flow and the node nearest the tumor is not necessarily the sentinel node. Failure to obtain dynamic images may lead to misdiagnosis of the sentinel node in a small percentage of patients.
Trust's refusal to fund trastuzumab was “arbitrary”
Authors: Clare Dyer
Journal: BMJ (2006)

An NHS trust that refused to pay for a woman with breast cancer to be treated with the monoclonal antibody trastuzumab (Herceptin) was accused of decision making that was “arbitrary in the extreme,” in the Court of Appeal this week.

David Pannick QC, counsel for Ann Marie Rogers, made the accusation as he launched an appeal against a High Court ruling last month upholding the stand taken by Swindon Primary Care Trust.

Ms Rogers, a 54 year old mother of three with HER2 breast cancer, has likened the trust's refusal to fund the £22 000 (€32 000; …
Intracellular pH regulation and proton transport by rabbit renal medullary collecting duct cells. Role of plasma membrane proton adenosine triphosphatase.
Authors: M L Zeidel, P Silva, J L Seifter
Journal: Journal of Clinical Investigation (1986)

Proton secretion in the renal medullary collecting duct is thought to occur via a luminal proton-ATPase. In order to determine what mechanism(s) participate in proton transport across medullary collecting duct (MCD) cells membranes, intracellular pH (pHi) regulation and proton extrusion rates were measured in freshly prepared suspensions of rabbit outer MCD cells. Cells were separated by protease digestion and purified by Ficoll gradient centrifugation. pHi was estimated fluorometrically using the entrapped intracytoplasmic pH indicator, 6-carboxyfluorescein. Proton extrusion rates were measured using a pH stat. The resting pHi of MCD cells was 7.19 +/- 0.05 (SE) in a nonbicarbonate medium of pH 7.30. When cells were acidified by exposure to acetate salts or by abrupt withdrawal of ammonium chloride, they exhibited pHi recovery to the resting pHi over a 5-min time-course. Depletion of greater than 95% of cellular ATP content by poisoning with KCN in the absence of glucose inhibited pHi recovery. ATP depletion inhibited proton extrusion from MCD cells. Treatment with N-ethylmaleimide also inhibited pHi recovery. In addition, cellular ATP content was dependent on transmembrane pH gradients, suggesting that proton extrusion stimulated ATP hydrolysis. Neither removal of extracellular sodium nor addition of amiloride inhibited pHi recovery. These results provide direct evidence that a plasma membrane proton-ATPase, but not a Na+/H+ exchanger, plays a role in proton transport and pHi regulation in rabbit MCD.
Ice-Pack Dermatosis
Authors: Sara E. West, Timothy H. McCalmont, Jeffrey P. North
Journal: JAMA Dermatology (2013)

IMPORTANCECold panniculitis is a self-limited condition, manifesting as erythematous plaques or nodules after cold exposure, that typically affects infants and children.Recently, a variant involving the lateral thighs of equestrians has been described.Since the original report of this variant, some confusion has arisen in the literature in which the terms equestrian cold panniculitis and equestrian perniosis are both used.Outside of this presentation, cold panniculitis in adults is exceedingly rare.OBSERVATIONS We describe 2 adult patients using ice-pack therapy for chronic back pain who developed erythematous, purpuric plaques at the site of ice-pack application.Histopathologic findings from both patients were similar and showed overlapping features of perniosis and cold panniculitis that closely resembled the pattern seen in cutaneous lupus erythematosus. CONCLUSIONS AND RELEVANCEIce-pack dermatosis is an uncommon cold-induced process that occurs in adults using long-term ice-pack therapy.The clinical manifestations include erythematous to purpuric plaques with a livedolike appearance and superficial ulceration.The histopathologic features resemble those seen in cutaneous lupus erythematosus with a superficial and deep perivascular and periadnexal dermatitis with increased dermal mucin and a superficial lobular panniculitis.
Abstract 5553: Liposomal rhenium by convection enhanced delivery for primary brain tumors
Authors: Andrew Brenner, Abram Trevino, Jessica Rogge, Beth Goins, Francis Giles, William Phillips
Journal: Cancer Research (2010)

Abstract Introduction: While adjuvant external beam radiation prolongs survival in glioblastoma, doses must be limited to approximately 60Gy secondary to lack of benefit and increased toxicity with higher doses. Despite maximum radiation, 90% of tumors recur at the original site. Convection enhanced delivery (CED) of radiation has the potential of administering higher doses locally to the tumor while reducing toxicity to normal brain parenchyma. Lipid nanocarriers offer the potential of distribution though the tumor as well as retention within the tumor. We hypothesized that a radionuclide liposome generated with a specially developed chemistry for loading a large quantity of rhenium, delivered by CED, would allow a higher dose of radiation to be delivered safely and effectively. Methods: Intracranial xenografts were established in nude rats with luciferase expressing U87 glioma cell line. To establish the correct volume of administration, liposomes were labeled with technetium99 and administered intratumorally by CED in volumes of 50 and 100ul at variable rates and imaged by SPECT/CT. Once volume and rate were established, an initial dose range finding study was performed with Re186 doses from 25 to 125uCi. The maximum tolerated dose was then assessed for efficacy as well as to confirm absence of toxicity. Tumor growth was followed by in vivo bioluminescent imaging and 7T MRI. Rats were sacrificed when moribund or when marked neurologic deficit was observed. Rat brains were evaluated by standard histologic methods for residual tumor, gliosis and necrosis. Results: Technetium liposomes in smaller volumes appeared to have better local retention with up to 60% retained at 22 hours post injection. Rats bearing U87 tumors treated with liposomal Rhenium186 tolerated the maximum administered dose of 125uCi (∼550Gy) without apparent toxicity, evidence of necrosis or gliosis. Efficacy was confirmed with rats treated at maximum dose, with all rats in the maximum dose continuing to survive and gain weight to 70 days post tumor inoculation, as compared to control rats which expired between 38 and 44 days. Conclusions: High doses (approx 550Gy) can be delivered to intracranial tumors in tumor bearing rats by CED of rhenium nanoliposomes. No evidence of neurotoxicity or histological changes suggestive of normal tissue injury are observed despite these very high doses. Rhenium liposomes delivered by CED show significant antiglioma activity with prolonged survival of treated tumor bearing rats. Further experiments are warranted to evaluate the potential of Rhenium 186 liposome in the treatment of glioblastoma and other primary brain tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5553.
High Impact of Oatp1a/1b Transporters on <i>In Vivo</i> Disposition of the Hydrophobic Anticancer Drug Paclitaxel
Authors: Evita van de Steeg, Anita van Esch, Els Wagenaar, Cornelia M.M. van der Kruijssen, Olaf van Tellingen, Kathryn E. Kenworthy, Alfred H. Schinkel
Journal: Clinical Cancer Research (2010)

Organic anion-transporting polypeptides (OATP) mediate the cellular uptake of a broad range of drugs. The hydrophobic anticancer drug, paclitaxel (PTX), was recently identified as a substrate for OATP1B3 in vitro. We investigated the role of Oatp1a/1b transporters in the pharmacokinetics of PTX in vivo, as well as their impact at different dose levels of PTX and methotrexate (MTX).Recently generated Slco1a/1b(-/-) (lacking all Oatp1a/1b transporters) and wild-type mice were intravenously dosed with 2, 10, or 50 mg/kg of PTX, or with 10, 50, or 500 mg/kg of MTX, and plasma and tissue drug concentrations were measured.In spite of its hydrophobicity, PTX systemic exposure (at 10 mg/kg) was increased by greater than 2-fold in Slco1a/1b(-/-) mice compared with wild-type, whereas PTX liver uptake was reduced by about 2-fold. Oatp1a/1b transporters displayed a high impact on PTX and MTX pharmacokinetics over a broad dose range. For MTX, even at 500 mg/kg, saturation of Oatp1a/1b was not observed, with a 3.4-fold increase in plasma and 30-fold decrease in liver levels in Slco1a/1b(-/-) mice compared with wild-type. Although beginning saturation of Oatp1a/1b was observed at the highest dose of PTX, plasma levels in Slco1a/1b(-/-) mice were still 1.7-fold increased and liver levels 1.5-fold decreased compared with wild-type.Oatp1a/1b transporters play a pronounced role in determining plasma levels and tissue distribution of MTX and PTX, thus affecting even highly hydrophobic drugs. Variation in OATP1A/1B transporter activity, due to genetic variation, inhibition, and/or tumor expression might affect toxicity and therapeutic efficacy of these anticancer drugs.
Targeting TORC2 in multiple myeloma with a new mTOR kinase inhibitor
Authors: Bao Hoang, Patrick Frost, Yijiang Shi, Eileen Belanger, Angelica Benavides, Gholam Pezeshkpour, Susanna Cappia, Tommasina Guglielmelli, Joseph Gera, Alan Lichtenstein
Journal: Blood (2010)
Ski Injuries-Reply
Authors: Jonathan B. Weisbuch
Journal: JAMA (1975)

In Reply.—  Drs Pope and Johnson have pointed out the epidemiologic differences between descriptive studies and analytic studies, and the value of the latter over the former in defining precise relationships between causal factors and, in this instance, traumatic events. However, they fail to point out that the importance of descriptive studies is to accumulate sufficient data with which causal hypotheses may be formulated. The major benefit of descriptive epidemiology is that studies of this type are inexpensive, do not require long-term follow-up, and can be carried out in a relatively short time by very few investigators. A complete discussion of the relative benefits of descriptive epidemiology, analytic epidemiology, and experimental studies may be found in either McMahon and Pugh ( The Principles of Epidemiology ) or Mauser and Bahn ( Epidemiology: An Introductory Text ), the two basic textbooks in the field.  The study carried out by Gutman, Wolf, and myself was descriptive,
Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era
Authors: Thomas M. Habermann, Sophia S. Wang, Matthew J. Maurer, Lindsay M. Morton, Charles F. Lynch, Stephen M. Ansell, Patricia Hartge, Richard K. Severson, Nathaniel Rothman, Scott Davis, Susan M. Geyer, Wendy Cozen, Stephen J. Chanock, James R. Cerhan
Journal: Blood (2008)