tbuckley/cabot-search huggingface dataset:
Interleukin-2 production by primary adult T cell leukemia tumor cells is macrophage dependent
Authors: Naomichi Arima, Yasuhisa Daitoku, Shiroh Hidakia, Kakushi Matsushita, Hideo Ohtsubo, Junko Fukumori, Hiromitsu Tanaka, Yusei Yamamoto, Kouji Fujimoto, Kaoru Onoue
Journal: American Journal of Hematology (1992)

Abstract We have investigated the cellular requirements for IL‐2 production by autocrine proliferating tumor cells from four patients with adult T cell leukemia (ATL). Cultures of these ATL cells both produced endogenous IL‐2 protein in the absence of added mitogen and proliferated at higher levels when exogenous recombinant IL‐2 was added. Depletion of macrophages in the tumor cell cultures resulted in a sharp decline in tumor cell IL‐2 production, while re‐addition of macrophages reconstituted this response. Macrophage‐derived factors including IL‐6 and IL‐1 also reconstituted IL‐2 production in these macrophage depleted cultures. These results raise the possibility that macrophages may play a central role in HTLV‐I mediated immortalization of T cells. © 1992 Wiley‐Liss, Inc.
Transcriptomic and phospho‐proteomic analyzes of erythroblasts expanded <i>in vitro</i> from normal donors and from patients with polycythemia vera
Authors: Todd Hricik, Giulia Federici, Ann Zeuner, Giuliana Alimena, Agostino Tafuri, Valentina Tirelli, Lilian Varricchio, Francesca Masiello, Fiorella Ciaffoni, Stefania Vaglio, Emanuel F. Petricoin, Gabriella Girelli, Ross L. Levine, Anna Rita F. Migliaccio
Journal: American Journal of Hematology (2013)

Erythropoiesis is a tightly regulated process which becomes decoupled from its normal differentiation program in patients with polycythemia vera (PV). Somatic mutations in JAK2 are commonly associated with this myeloid proliferative disorder. To gain insight into the molecular events that are required for abnormally developing erythroid cells to escape dependence on normal growth signals, we performed in vitro expansion of mature erythroblasts (ERY) from seven normal healthy donors and from seven polycythemic patients in the presence of IL3, EPO, SCF for 10, 11, or 13 days. Normal ERYs required exposure to the glucocorticoid dexamethasone (Dex) for expansion, while PV-derived ERYs expanded in the absence of dexamethasone. RNA expression profiling revealed enrichment of two known oncogenes, GPR56 and RAB4a, in PV-derived ERYs along with reduced expression levels of transcription factor TAL1 (ANOVA FDR < 0.05). While both normal and polycythemic-derived ERYs integrated signaling cascades for growth, they did so via different signaling pathways which are represented by their differential phospho-profiles. Our results show that normal ERYs displayed greater levels of phosphorylation of EGFR, PDGFRβ, TGFβ, and cKit, while PV-derived ERYs were characterized by increased phosphorylation of cytoplasmic kinases in the JAK/STAT, PI3K, and GATA1 pathways. Together these data suggest that PV erythroblast expansion and maturation may be maintained and enriched in the absence of dexamethasone through reduced TAL1 expression and by accessing additional signaling cascades. Members of this acquired repertoire may provide important insight into the pathogenesis of aberrant erythropoiesis in myeloproliferative neoplasms such as polycythemia vera.
Transferrin conjugation confers mucosal molecular targeting to a model HIV-1 trimeric gp140 vaccine antigen
Authors: J.F.S. Mann, D. Stieh, K. Klein, D.S. Miranda de Stegmann, M.P. Cranage, R.J. Shattock, P.F. McKay
Journal: Journal of Controlled Release (2011)

The generation of effective immune responses by mucosal vaccination without the use of inflammatory adjuvants, that compromise the epithelial barrier and recruit new cellular targets, is a key goal of vaccines designed to protect against sexually acquired pathogens. In the present study we use a model HIV antigen (CN54gp140) conjugated to transferrin (Tf) and evaluate the ability of the natural transferrin receptor CD71 to modulate immunity. We show that the conjugated transferrin retained high affinity for its receptor and that the conjugate was specifically transported across an epithelial barrier, co-localizing with MHC Class II(+) cells in the sub-mucosal stroma. Vaccination studies in mice revealed that the Tf-gp140 conjugate elicited high titres of CN54gp140-specific serum antibodies, equivalent to a systemic vaccination, when conjugate was applied topically to the nasal mucosae whereas gp140 alone was poorly immunogenic. Moreover, the Tf-gp140 conjugate elicited both IgG and IgA responses and significantly higher gp140-specific IgA titre in the female genital tract than unconjugated antigen. These responses were achieved after mucosal application of the conjugated protein alone, in the absence of any pro-inflammatory adjuvant and suggest a potentially useful and novel molecular targeting approach, delivering a vaccine cargo to directly elicit or enhance pathogen-specific mucosal immunity.
SUICIDE ATTEMPT WITH WARFARIN, A BISHYDROXYCOUMARIN-LIKE RODENTICIDE
Authors: Roy W. Holmes
Journal: JAMA (1952)

Through the ages the rat, which has caused untold amounts of sickness and death as well as property damage that far exceeds human imagination, has been a major scourge of mankind. Investigators throughout the world have searched for the ideal rat poison, which, according to O'Connor,<sup>1</sup>must have the following characteristics: 1. It must be surely effective in baits of small quantity so that its presence is not detected by the rodent. 2. The finished bait must not excite shyness of the rat population so that the necessity for prebaiting is avoided. 3. The manner of death must be such that surviving rats will not become suspicious and will remain on the premises eating of the bait until they, too, die. 4. The poison must be species specific unless its use can be made safe for man and domestic animals by some other means. This ideal rodenticide proved to
Dual-Phase F-18 FDG PET/CT Scanning in the Suspicion of Relapse of Ovarian Neoplasia
Authors: Daniele Penna, Teresio Varetto, Désirée Deandreis, Giancarlo Castellano, Gianni Bisi
Journal: Clinical Nuclear Medicine (2009)

A 72-year-old woman who was treated for a poorly differentiated ovarian adenocarcinoma (pT4,M1) underwent FDG-PET/CT scan for suspicion of pararectal disease relapse seen on a CT scan. The pararectal lesion did not show any significant uptake (SUVmax 2.0), but an abnormal unexpected uptake (SUVmax 4.0) was observed in the right pelvic region. A delayed FDG PET/CT scan focused on the pelvic region was performed. On delayed images, the pararectal lesion showed a significant (80%) SUVmax increase (2 vs. 3.6), becoming a clearly positive PET scan. On the other hand, the pelvic lesion showed a stable SUVmax (4.0), but an unchanged anatomic localization of this finding allowing to be differentiated from intestinal activity. Both lesions were confirmed as malignant on histopathological specimens. In conclusion, dual-phase PET acquisition can be helpful in the characterization of an abdominal-pelvic mass.
DERMATITIS DUE TO MERCURY FOLLOWING AMALGAM DENTAL RESTORATIONS
Authors: J. THOMSON, J. A. RUSSELL
Journal: British Journal of Dermatology (1970)

SUMMARY. A patient is described who developed an urticarial and later a blistered weeping eruption on her face, anterior trunk and on her limbs, predominantly in the flexures, following silver amalgam dental treatment. This eruption was associated with moderately severe systemic effects. Patch tests confirmed that she was hypersensitive to mercury. The literature on previous reports is reviewed and a short account given of the likely degree of exposure to mercury following amalgam restoration.
The same site on the integrase-binding domain of lens epithelium–derived growth factor is a therapeutic target for MLL leukemia and HIV
Authors: Marcelo J. Murai, Jonathan Pollock, Shihan He, Hongzhi Miao, Trupta Purohit, Adam Yokom, Jay L. Hess, Andrew G. Muntean, Jolanta Grembecka, Tomasz Cierpicki
Journal: Blood (2014)
A national long-term care program for the United States. A caring vision. The Working Group on Long-term Care Program Design, Physicians for a National Health Program
Authors: C. Harrington
Journal: JAMA (1991)

The financing and delivery of long-term care (LTC) need substantial reform. Many cannot afford essential services; age restrictions often arbitrarily limit access for the nonelderly, although more than a third of those needing care are under 65 years old; Medicaid, the principal third-party payer for LTC, is biased toward nursing home care and discourages independent living; informal care provided by relatives and friends, the only assistance used by 70% of those needing LTC, is neither supported nor encouraged; and insurance coverage often excludes critically important services that fall outside narrow definitions of medically necessary care. We describe an LTC program designed as an integral component of the national health program advanced by Physicians for a National Health Program. Everyone would be covered for all medically and socially necessary services under a single public plan, federally mandated and funded but administered locally. An LTC payment board in each state would contract directly with providers through a network of local public agencies responsible for eligibility determination and care coordination. Nursing homes, home care agencies, and other institutional providers would be paid a global budget to cover all operating costs and would not bill on a per-patient basis. Alternatively, integrated provider organizations could receive a capitation fee to cover a broad range of LTC and acute care services. Individual practitioners could continue to be paid on a fee-for-service basis or could receive salaries from institutional providers. Support for innovation, training of LTC personnel, and monitoring of the quality of care would be greatly augmented. For-profit providers would be compensated for past investments and phased out. Our program would add between $18 billion and $23.5 billion annually to current spending on LTC. Polls indicate that a majority of Americans want such a program and are willing to pay earmarked taxes to support it.
Accessory Cardiac Bronchus
Authors: Eric S. White
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

A 57-year-old man underwent high-resolution computed tomography (HRCT) scanning and bronchoscopy as part of an evaluation for dyspnea and exercise intolerance.Physical examination was without abnormalities.Incidental note was made of an air-filled structure (black arrow) medial to the bronchus intermedius (BI) on HRCT (Figure 1).Bronchoscopy revealed normal airways, except for an accessory (cardiac) bronchus (ACB) arising from the BI (Figure 2).ACB occur in up to 0.5% of the general population and usually end as a blind pouch.They may also be associated with small amounts of pulmonary parenchyma.ACB are almost always an incidental finding, although they may be a reservoir of infectious material, source of hemoptysis, or origin of malignancy.The most common location of ACB is the inferomedial wall of the right mainstem bronchus, but can be found arising from the BI as seen in this patient.
Abstract P1-08-04: Doses of Selective Estrogen Receptor Modulations (SERMS) Required for Prevention and Therapy of Chemically-Induced Mammary Cancers
Authors: BM Heckman-Stoddard, CJ Grubbs, K Johnson, RA. Lubet
Journal: Cancer Research (2010)

Abstract Selective Estrogen Receptor Modulators (SERMs) interfere with the activation of the estrogen receptor. SERMs have been shown to be effective for both treatment and prevention of breast cancer. Here we examine the ability of tamoxifen and arzoxifene, a more easily absorbed form of raloxifene, to prevent mammary tumors at a significantly lower dosage than those used for treatment. For prevention studies, female Sprague-Dawley rats (50 days of age) were injected with a single i.v. dose of MNU resulting in the development of multiple ER-positive mammary tumors beginning 7 weeks after carcinogen treatment. Rats were administered the preventive agent beginning five days after carcinogen administration. When the agents were tested at does varying between 0.15-3.3 ppm in the diet, both agents caused a dose dependent increase in preventive activity. The highest doses of tamoxifen (3.3 ppm) and arzoxifene (3.0 ppm) both decreased tumor multiplicity greater than 90%. Both of these doses are less than one-fifth the human equivalent dose (HED) based on standard FDA scaling factors. Both doses also resulted in substantial decreases in mammary gland development. These dosages were then used in a therapy setting to compare the efficacy. For these studies, MNU treated rats were allowed to develop their first palpable mammary tumor (70-150 mm2) before initiating treatment. Tumor growth or regression was followed by caliper measurements. Neither of the preventive doses of these SERMs exhibited therapeutic activity although substantially higher doses of tamoxifen (33 or 100 ppm) were relatively effective. These results are in contrast to our prior findings with other classes of agents (RXR agonists, EGFR inhibitors, and aromatase inhibitors) in which highly effective preventive doses were as effective as therapeutic doses in this model. These results demonstrate the unique dose differential regarding prevention and therapy with SERMs. Microarray analysis of tumors treated for 5 days with tamoxifen at doses of 3.3ppm or 100ppm reveals overlapping significant gene changes of similar magnitude in comparison to control treated tumors although there were significant gene changes seen at the therapeutic dose which were not observed at the lower dose. These studies raise two questions: 1) whether this class of agents might be used at significantly lower doses in a pure prevention setting as contrasted with a therapeutic setting where they were initially defined; 2) are there gene expression changes which might be used to help identify this differential dosing for prevention vs. therapy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-08-04.
September 2002 Extramurally Speaking
Journal: Environmental Health Perspectives (2002)

The search to understand human health effects of environmental agents at all levels-molecular, cellular, organ, individual, and population-is hampered by a lack of specific model systems in which to carry out scientific investigations.In the past, assessment of potential adverse health effects of chemicals has been accomplished largely by tests utilizing laboratory animals.Both eukaryotic and prokaryotic cell culture models have been developed to elucidate molecular mechanisms by which physical and chemical environmental exposures activate or deregulate molecular pathways leading to disease outcomes.However, methods and models that can be employed to investigate how similar biological pathways are affected by exposures related to the social environment have not been as clearly defined.The NIEHS is initiating programs that foster the use of animal models to study how social environmental stressors may activate or stimulate molecular pathways that can lead to disease states.Recent NIEHS scientific retreats have featured sessions on animal models of physical and social environmental stress (see, for example, "DERT Annual Scientific Retreat," EHP 110:A207 [2002], available online at http://ehpnet1.niehs.nih.gov/docs/2002/110-4/extram-speaking.html).Topics discussed during these sessions have included behavioral, neurochemical, and immunological effects of both social and physical stressors.For example, atherosclerosis induction by moderate hyperlipoproteinemia in grouphoused cynomolgus macaques differs markedly in animals of dominant versus subordinate social status.Both rodent and primate studies reveal differential susceptibility to adenovirus infection and subsequent development of a biologically definable infection that is dependent on rank or social stature in the dominance hierarchy of the animal colonies.Such results suggest that social or psychosocial stress can affect immune function and lead to increased vulnerability to illness.These interactions may be crucial in addressing health problems associated with particular populations, such as individuals or communities of low socioeconomic status.NIEHS-supported research assessing the contributions of the social environment (neighborhood characteristics, socioeconomic status, psychosocial stress, occupational hierarchy, race and gender discrimination, and social trust) has not focused on the use of animal models.The recent NIEHS-led trans-NIH solicitation ES-02-009, "Centers for Population Health and Health Disparities," is the first specific initiative that seeks to stimulate the use of animal models in investigating the contributions of social environmental factors to the activation of molecular pathways predisposing or leading to disease development.In addition, individual investigators are now actively encouraged to develop and utilize a variety of animal models to enhance our understanding of the biological and behavioral mechanisms by which both social and physical environmental influences can affect health status.
Effects of the Intracoronary Infusion of Cocaine on Left Ventricular Systolic and Diastolic Function in Humans
Authors: William R. Pitts, Wanpen Vongpatanasin, Joaquin E. Cigarroa, L. David Hillis, Richard A. Lange
Journal: Circulation (1998)

In dogs, a large amount of intravenous cocaine causes a profound deterioration of left ventricular (LV) systolic function and an increase in LV end-diastolic pressure. This study was done to assess the influence of a high intracoronary cocaine concentration on LV systolic and diastolic function in humans.In 20 patients (14 men and 6 women aged 39 to 72 years) referred for cardiac catheterization for the evaluation of chest pain, we measured heart rate, systemic arterial pressure, LV pressure and its first derivative (dP/dt), and LV volumes and ejection fraction before and during the final 2 to 3 minutes of a 15-minute intracoronary infusion of saline (n=10, control subjects) or cocaine hydrochloride 1 mg/min (n=10). No variable changed with saline. With cocaine, the drug concentration in blood obtained from the coronary sinus was 3.0+/-0.4 (mean+/-SD) mg/L, similar in magnitude to the blood cocaine concentration reported in abusers dying of cocaine intoxication. Cocaine induced no significant change in heart rate, LV dP/dt (positive or negative), or LV end-diastolic volume, but it caused an increase in systolic and mean arterial pressures, LV end-diastolic pressure, and LV end-systolic volume, as well as a decrease in LV ejection fraction.In humans, the intracoronary infusion of cocaine sufficient in amount to achieve a high drug concentration in coronary sinus blood causes a deterioration of LV systolic and diastolic performance.
Revascularization Methods for Coronary Artery Disease
Authors: Harry W. Donias
Journal: JAMA (2001)

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14. rAAV2 Integration Junctions Isolated without In Vivo Selection Bias Show a Preference to 5′ Regions of Open Reading Frames
Authors: Fayaz R. Khazi, Alexander Schlachterman, Katherine A. High
Journal: Molecular Therapy (2005)

Recombinant adeno-associated viral vectors have been successfully used in animal models for stable and long-term transgene expression. The vector genomes which contribute to the majority of transgene expression persist mainly as extra-chromosomal episomes. A low frequency of integration events has also been observed in quiescent hepatocytes as well as cultured cells. Studies conducted in the wake of a report of retroviral insertional mutagenesis indicate that rAAV2 genomes integrate preferentially in active regions of the host chromosomes. Todate isolation and analysis of rAAV2 integration junctions has been conducted either under genetic or antibiotic selection to accommodate technical limitations. Genetic selection introduces a bias towards actively dividing cells and hence over represent integration events in actively transcribed regions of the genome, whereas cloning based methods under-represent difficult-to-clone or repetitive DNA.
Re-entrant ventricular arrhythmias in the late myocardial infarction period. 4. Mechanism of action of lidocaine.
Authors: N El-Sherif, B J Scherlag, R Lazzara, R R Hope
Journal: Circulation (1977)

The effect of lidocaine on re-entrant ventricular arrhythmias (RVA) was studied in dogs 3-7 days following ligation of the anterior descending coronary artery; direct recordings were made of the re-entrant pathway (RP) from the epicardial surface of the infarction zone (IZ). Lidocaine in a therapeutic dose consistently prolonged refractoriness of potentially RP(s) in the IZ and produced a higher degree of conduction block at a constant heart rate. Conduction in the adjacent normal zone was not affected. The impairment of conduction induced by lidocaine in the RP was directly related to its ability to abolish re-entrant ventricular beats and tachycardia. Gradual slowing of conduction in the RP consistently developed before abolition: lengthening of coupling of extrasystolic beats in surface leads and gradual slowing of ventricular tachycardia rate occurred. The termination of re-entry was characteristically associated with complete block in the RP. A "selectivity hypothesis" for the antiarrhythmic action of lidocaine is proposed.