tbuckley/cabot-search huggingface dataset:
Health care in Moscow.
Authors: M Ryan
Journal: BMJ (1993)

In the Russian Federation privatisation is affecting the health care sector as much as it is industry and commerce. That the general public support the transfer of state clinics to the private sector is a mark of their dissatisfaction with the old state run system. Doctors too see better opportunities to practise good medicine and be paid better for doing so. In Moscow the health department has set up a commission to license all clinics providing treatment, which should ensure standards of safety, training, and equipment. The Russian Federation is also trying to establish a medical insurance system to cover its citizens for health care, but in Moscow and elsewhere its implementation has been delayed by arguments and bureaucracy. In the meantime the health of Muscovites remains poor, with a high incidence of birth defects, and illnesses among the young.
Abstract P5-15-03: Prediction of positive resection margins in patients with non-palpable breast cancer
Authors: MW Barentsz, EL Postma, T van Dalen, MA van den Bosch, M Hui, PD Gobardhan, AJ Witkamp, PJ van Diest, J van Gorp, R van Hillegersberg, HM Verkooijen
Journal: Cancer Research (2013)

Abstract Background Obtaining tumor free resection margins is essential in patients undergoing breast conserving surgery. Several risk factors associated with positive margins are described in literature. We developed a prediction model to predict positive resection margins in patients undergoing breast conserving surgery of non-palpable lesions. Methods A total of 576 patients with non-palpable invasive breast cancer underwent breast conserving surgery at five different hospitals in the Netherlands. A prediction model for positive resection margins was built using multivariate regression analysis and internally validated by bootstrapping. Results Positive resection margins were present in 69/576 (12%) patients. Factors associated with positive margins included microcalcifications on mammography (OR 1.8, 1.0-3.2), tumor not visible on ultrasound (OR 2.6, 1.2-5.6), presence of DCIS (OR 2.3, 1.3-4.0), multifocality (OR 3.5, 1.0-12.1), caudal location in the breast (OR 1.9, 1.1-3.5), and invasive tumor size (OR 1.83, 1.6-2.7). Together, these factors were able to moderately discriminate between patients with positive versus negative margins (area under the ROC 0.71, 95% CI 0.648 – 0.780). After internal validation the discrimination was slightly lower with an AUC of 0.694. Prevalence of positive margins was 5.2% in the highest risk quintile versus 26.3% in the lowest quintile. Conclusion A model predicting positive resection margins after breast conserving surgery in non-palpable breast cancer was built. This model is moderately able to differentiate between women with high versus low risk of positive margins, and may be useful for surgical planning (eg. preoperative MRI) and informing of patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-15-03.
Chronic Idiopathic Hypertrophic Osteoarthropathy
Authors: Morris Berk
Journal: New England Journal of Medicine (1952)

THE clinician is often confronted with clubbed fingers in an otherwise healthy person. However, idiopathic hypertrophic osteoarthropathy, or clubbing with extensive bone and joint changes without underlying etiologic disease, is a rarity. Only recently has this subject been clarified,1 the literature having been confused by a variety of titles such as "familial acromegaloid osteosis," "idiopathic familial generalized osteophytosis," "hypertrophic pulmonary osteoarthropathy without primary disease" and "acropachydermia with pachyperiostitis." As mentioned by Camp and Scanlan,1 these terms have been used because of certain characteristics of the disease, such as its familial tendency, its superficial resemblance to acromegaly and its similarity to . . .
Botanical Medicines — The Need for New Regulations
Authors: Donald M Marcus, Arthur P Grollman
Journal: New England Journal of Medicine (2002)

In 2001, $17.8 billion was spent in the United States on dietary supplements, $4.2 billion of it for herbs and other botanical remedies.1 The popularity of these products has increased over the past decade, probably stimulated by sharp increases in prices of prescription drugs, restricted access to physicians imposed by managed care, media reports of adverse effects of prescription drugs, and, most important, the enactment in 1994 of the Dietary Supplement and Health Education Act (DSHEA). By broadly defining herbs and other botanicals as “dietary supplements,” the DSHEA substantially altered the definitions, standards, and mechanisms under which claims about the . . .
Aspirin induced asthma
Authors: Indu Sivanandan, Stephen M Robinson
Journal: BMJ (2004)

EDITOR—The prevalence of aspirin induced asthma on oral provocation testing in the systematic review by Jenkins et al was determined at 21%, which is noticeably higher than verbal history (2-3%) and recent reviews (10%).1–3 The clinical relevance of this finding is not explained. What was the degree of bronchospasm? In …
A Transgenic Mouse Model of Plasma Cell Malignancy Shows Phenotypic, Cytogenetic, and Gene Expression Heterogeneity Similar to Human Multiple Myeloma
Authors: Kristin L.M. Boylan, Mary A. Gosse, Sarah E. Staggs, Siegfried Janz, Suzanne Grindle, Geoffrey S. Kansas, Brian G. Van Ness
Journal: Cancer Research (2007)

Abstract Multiple myeloma is an incurable plasma cell malignancy for which existing animal models are limited. We have previously shown that the targeted expression of the transgenes c-Myc and Bcl-XL in murine plasma cells produces malignancy that displays features of human myeloma, such as localization of tumor cells to the bone marrow and lytic bone lesions. We have isolated and characterized in vitro cultures and adoptive transfers of tumors from Bcl-xl/Myc transgenic mice. Tumors have a plasmablastic morphology and variable expression of CD138, CD45, CD38, and CD19. Spectral karyotyping analysis of metaphase chromosomes from primary tumor cell cultures shows that the Bcl-xl/Myc tumors contain a variety of chromosomal abnormalities, including trisomies, translocations, and deletions. The most frequently aberrant chromosomes are 12 and 16. Three sites for recurring translocations were also identified on chromosomes 4D, 12F, and 16C. Gene expression profiling was used to identify differences in gene expression between tumor cells and normal plasma cells (NPC) and to cluster the tumors into two groups (tumor groups C and D), with distinct gene expression profiles. Four hundred and ninety-five genes were significantly different between both tumor groups and NPCs, whereas 124 genes were uniquely different from NPCs in tumor group C and 204 genes were uniquely different from NPCs in tumor group D. Similar to human myeloma, the cyclin D genes are differentially dysregulated in the mouse tumor groups. These data suggest the Bcl-xl/Myc tumors are similar to a subset of plasmablastic human myelomas and provide insight into the specific genes and pathways underlying the human disease. [Cancer Res 2007;67(9):4069–78]
Abstract 4873: Functional interactions between lysine 20 methylation and lysine 16 acetylation on histone H4 in DNA damage responses
Authors: Kuei-Yang Hsiao, Craig Mizzen
Journal: Cancer Research (2010)

Abstract Individual histone post-translational modifications have been implicated in regulating many cellular events. Modifications can occur at high densities in the N-terminal tail domains of core histones, enabling the possibility that combinations of modifications regulate chromatin processes differently than modifications occurring individually. However, surprisingly little is known about the nature and functions of multi-site histone modification. This study investigates functional interactions between acetylation of lysine 16 (K16ac) and methylation of lysine 20 (K20me), two modifications that frequently occur together on molecules of histone H4. Methylation state-specific binding of p53-binding protein 1 (53BP1) to dimethyl K20 H4 (K20me2) and the formation of 53BP1 nuclear foci near double strand breaks are early events in DNA damage responses (DDR) that provide a platform for the assembly of downstream effectors. Since global levels of K20me2 are relatively stable and are established independently of DNA damage, we propose that reversible changes in the levels of K16ac co-modification act like a dynamic switch to modulate DDR responses mediated by K20me2. Analyses of the interaction of the K20me2 binding domain of 53BP1 with H4 peptides in vitro reveal that K16ac co-modification attenuates specific recognition of K20me1/2 by 53BP1. The possibility that K16ac and K20me2 interact functionally in vivo is demonstrated by our finding that K16 deacetylation accompanies the induction of H2AX phosphorylation, a well-known marker for DDR, following DNA damage by either UV irradiation or bleomycin treatment. Moreover, the effects of expressing K16 mutants of H4 and inhibition of histone deacetylases on 53BP1 foci formation induced by DNA damage are consistent with our hypothesis that K16ac co-modification negatively regulates the formation of 53BP1 foci. DDR mechanisms are frequently deregulated in cancer cells. Further investigation of the role of H4 modifications in DDR will enhance our understanding of how genome integrity is maintained in normal cells and may identify novel targets for future therapies. 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 4873.
Role of Adenosine Receptors in the Paradoxic Bradycardia Response of Rats to Inferior Vena Cava Occlusion During an Infusion of Isoproterenol
Authors: Menashe B. Waxman, John A. Asta
Journal: Circulation (1998)

Background —In susceptible humans, vasodepressor reactions are induced by restriction of venous return (upright tilting) and administration of isoproterenol. Because paradoxic bradycardia is a major manifestation of vasodepressor reactions, and allowing for extrapolation between paradoxic bradycardia in rats and vasodepressor reactions, we examined whether adenosine receptors mediate the paradoxic bradycardia reaction. Methods and Results —Paradoxic bradycardia was induced in rats by inferior vena cava occlusion during an isoproterenol infusion. We studied whether dipyridamole, an adenosine transport inhibitor, and aminophylline (nonselective) or DPCPX (selective) A 1 antagonists augmented or inhibited paradoxic bradycardia, respectively, during inferior vena cava occlusion. The maximum changes in R-R during 60 seconds of inferior vena cava occlusion were that (1) in control, the rate accelerated (ΔR-R, −9.7±0.8 ms, P &lt;0.001); (2) during isoproterenol (0.8 μg · min −1 ), paradoxic bradycardia occurred (ΔR-R, +92.0±32.0 ms, P &lt;0.001); (3) during isoproterenol but after dipyridamole, paradoxic bradycardia occurred at a much lower dose of isoproterenol (0.2 μg · min −1 ), and the magnitude was increased at all doses (at 0.8 μg · min −1 isoproterenol, ΔR-R, +195.6±27.6 ms, P &lt;0.001 versus isoproterenol alone, ΔR-R, +92.0±32 ms); (4) during isoproterenol and dipyridamole, atropine did not block paradoxic bradycardia, but cervical vagotomy inhibited paradoxic bradycardia (ΔR-R, +5.6±1.8 ms, P &lt;0.001 compared with isoproterenol and dipyridamole alone); and (5) during isoproterenol alone, aminophylline or DPCPX blocked paradoxic bradycardia (ΔR-R, −5.4±1.0 ms, and ΔR-R, −2.6±0.5 ms, respectively, each P &lt;0.001 compared with isoproterenol alone). Conclusions —The adenosine A 1 receptor mediates the paradoxic bradycardia reflex during inferior vena cava occlusion in the face of isoproterenol via vagal afferents.
[763] CRITICAL EVALUATION OF CANDIDATE GENE POLYMORPHISMS IN THE DEVELOPMENT OF ALCOHOLIC LIVER CIRRHOSIS
Authors: F. Stickel, C. Oesterreicher, V. Schneider, J. Halangk, T. Berg, E. Patsenker, N. Homann, C. Hellerband, A. Kolb, H. Friess, D. Schuppan, H.K. Seitz
Journal: Journal of Hepatology (2007)
Britain's housing is unfit to live in
Authors: L Dillner
Journal: BMJ (1994)

One in 13 homes in Britain is unfit for human habitation and another one in six needs urgent repairs, says a report from the National Housing Forum published this week. The report, which draws on government statistics, focuses on Britain's 19 million private homes and says that at least pounds sterling 70bn is needed to bring properties up to the standard expected by building societies for mortgage purposes. The rate of clearance of old properties is so slow - one in four is over 80 years old - that most houses will still be standing in the year 3000.

The National Housing Forum, which represents charities, local government groups, and professional …
The development of equivalence as a mechanism to improve prison healthcare
Authors: Alex Till, Andrew Forrester, Tim Exworthy
Journal: Journal of the Royal Society of Medicine (2014)

Over the past two decades landmark reforms havetaken place in England and Wales to moderniseprison mental healthcare. Spearheaded by thereport Patient or Prisoner?, subsequent Departmentof Health guidance The future organisation of prisonhealthcare and Changing the Outlook, brought thestate of prison healthcare to the front of the politicalagenda with two essential principles: continuity ofcare and equality.
Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse
Authors: Pilar Muñoz, María Mittelbrunn, Hortensia de la Fuente, Manuel Pérez-Martínez, Angélica García-Pérez, Adriana Ariza-Veguillas, Fabio Malavasi, Mercedes Zubiaur, Francisco Sánchez-Madrid, Jaime Sancho
Journal: Blood (2008)
Paradoxical effects of short- and long-term interleukin-6 exposure on liver injury and repair
Authors: Xiaoling Jin, Teresa A. Zimmers, Eduardo A. Perez, Robert H. Pierce, Zongxiu Zhang, Leonidas G. Koniaris
Journal: Hepatology (2006)

Interleukin-6 (IL-6) is an important mediator of liver regeneration and repair that is also elevated in chronic liver diseases, including fatty liver of obesity and cirrhosis. IL-6 has been reported both to delay and accelerate liver regeneration. We examined the effects on liver injury and regeneration of a continuous administration of exogenous IL-6 to mice by injection of an IL-6–expressing CHO-cell line in athymic nude mice and by osmotic mini-pump delivery of recombinant murine IL-6. Short-term IL-6 administration (1-2 days) accelerated early recovery of liver mass, whereas more long-term administration (5-7 days) markedly impaired liver regeneration. Similarly, short-term IL-6 treatment increased hepatic resistance to the lethal effects of the Fas agonist Jo-2, but on more prolonged IL-6 exposure the Jo-2 resistance vanished. IL-6 administration initially induced expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, correlating with protection against Fas-mediated cell death. More prolonged IL-6 administration, however, resulted in marked induction of the pro-apoptotic protein Bax. This result coincided with increased activation of the type II or intrinsic, mitochondrial path to cell death, manifested by increased caspase-9 activation and increased cytochrome c release after Jo-2 exposure. These data demonstrate that IL-6 can function acutely to improve hepatic regeneration and repair, but that more chronic exposure not only abolishes the protective effects of IL-6, but actually sensitizes the liver to injury and death. In conclusion, elevated IL-6 in certain chronic liver diseases contributes to an increased likelihood of liver failure after injury. (Hepatology 2006;43:474–484.)
Abstract 805: The role of aldo-keto reductases and estrogen signalling in acquired anthracycline resistance
Authors: Simon Chewchuk, Amadeo M. Parissenti
Journal: Cancer Research (2012)

Abstract Breast cancer is the second leading cause of death from cancer in North American women. The disease can be difficult to treat by adjuvant or neoadjuvant chemotherapy because of intrinsic or acquired resistance to chemotherapy agents. To better understand the mechanisms for acquired resistance to the anthracycline class of chemotherapy agents in breast cancer, a series of MCF-7 breast tumour cell lines have been developed that exhibit progressive resistance to epirubicin (MCF-7EPI cells) or to doxorubicin (MCF-7DOX2 cells). Following mRNA microarray analysis, several genes were identified whose expression was associated with the acquisition of anthracycline resistance. Among these were several Aldo-keto Reductases (AKRs) responsible for estrogen synthesis from estrone and anthracycline detoxification to 13-hydroxymetabolites. AKR 1C3 showed more than a 10-fold increase in expression in anthracycline-resistant breast tumour cells. We hypothesized that the over-expression of AKR 1C3 would lead to both increased drug detoxification and an increase in estrogen synthesis. This would result in increased tumour cell survival and growth in the presence of anthracyclines. Recently, we observed that estrogen levels were, in fact, increased as cells became anthracycline-resistant. In contrast, the expression of estrogen receptor ≤ (ESR1) was reduced by 2- to 5-fold at the gene level and 2- to 20- fold at the protein level, with a concomitant reduction in the estrogen-dependent expression of Bcl-2 and Cyclin D1. Diminished Bcl-2 and cyclin D1 expression would be expected to reduce the growth rate of the cells, a hypothesis we have confirmed in cell culture experiments. Taken together, our findings suggest that selection for anthracycline resistance in breast tumour cells results in alterations in AKR expression, resulting in enhanced detoxification of doxorubicin, the promotion of estrogen biosynthesis, and the reduced estrogen-dependent expression of Bcl-2 and cyclin D1. The reduced expression of Bcl-2 and cyclin D1 blunts the growth rate of anthracycline-resistant cells, which would further increase the ability of these cells to survive in the presence of anthracyclines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 805. doi:1538-7445.AM2012-805
A genome-wide RNAi screen identifies proteins modulating aberrant FLT3-ITD signaling
Authors: A Caldarelli, J P Müller, M Paskowski-Rogacz, K Herrmann, R Bauer, S Koch, A K Heninger, D Krastev, L Ding, S Kasper, T Fischer, M Brodhun, F-D Böhmer, F Buchholz
Journal: Leukemia (2013)

Fms-like tyrosine kinase-3 is a commonly mutated gene in acute myeloid leukemia, with about one-third of patients carrying an internal-tandem duplication of the juxtamembrane domain in the receptor (FLT3-ITD). FLT3-ITD exhibits altered signaling quality, including aberrant activation of STAT5. To identify genes affecting FLT3-ITD-mediated STAT5 signaling, we performed an esiRNA-based RNAi screen utilizing a STAT5-driven reporter assay. Knockdowns that caused reduced FLT3-ITD-mediated STAT5 signaling were enriched for genes encoding proteins involved in protein secretion and intracellular protein transport, indicating that modulation of protein transport processes could potentially be used to reduce constitutive STAT5 signaling in FLT3-ITD-positive cells. The relevance of KDELR1, a component involved in the Golgi-ER retrograde transport, was further analyzed. In FLT3-ITD-expressing leukemic MV4-11 cells, downregulation of KDELR1 resulted in reduced STAT5 activation, proliferation and colony-forming capacity. Stable shRNA-mediated depletion of KDELR1 in FLT3-ITD-expressing 32D cells likewise resulted in reduced STAT5 signaling and cell proliferation. Importantly, these cells also showed a reduced capacity to generate a leukemia-like disease in syngeneic C3H/HeJ mice. Together our data suggest intracellular protein transport as a potential target for FLT3-ITD driven leukemias, with KDELR1 emerging as a positive modulator of oncogenic FLT3-ITD activity.
Blood Pressure and Skin Color
Authors: Henry S. Kahn
Journal: JAMA (1991)

To the Editor.—  Klag et al1have presented interesting data about the distribution of blood pressure in US blacks. However, their analysis may have failed to consider the striking effect that the city of residence had on their blood pressure observations. The mean blood pressure in Savannah, Ga, for example, was 10/6 mm Hg higher than it was in Pueblo, Colo (Klag et al, Table 2, p 600). By way of comparison, there is a somewhat smaller difference in mean blood pressures, only 5/5 mm Hg, between subjects at the highest and lowest quartiles of skin color (unadjusted data; Table).  Since the city of residence was associated both with skin color (the risk factor under examination) and with blood pressure (the outcome variable), it would have been appropriate for Klag et al to include the city of residence among the variables in their multivariate analysis. It is not clear
Engineering Dendritic Cells to Enhance Cancer Immunotherapy
Authors: Jeanette E Boudreau, Aude Bonehill, Kris Thielemans, Yonghong Wan
Journal: Molecular Therapy (2011)

Cancer immunotherapy aims to establish immune-mediated control of tumor growth by priming T-cell responses to target tumor-associated antigens. Three signals are required for T-cell activation: (i) presentation of cognate antigen in self MHC molecules; (ii) costimulation by membrane-bound receptor-ligand pairs; and (iii) soluble factors to direct polarization of the ensuing immune response. The ability of dendritic cells (DCs) to provide all three signals required for T-cell activation makes them an ideal cancer vaccine platform. Several strategies have been developed to enhance and control antigen presentation, costimulation, and cytokine production. In this review, we discuss progress toward developing DC-based cancer vaccines by genetic modification using RNA, DNA, and recombinant viruses. Furthermore, the ability of DC-based vaccines to activate natural killer (NK) and B-cells, and the impact of gene modification strategies on these populations is described. Clinical trials using gene-modified DCs have shown modest results, therefore, further considerations for DC manipulation to enhance their clinical efficacy are also discussed. Cancer immunotherapy aims to establish immune-mediated control of tumor growth by priming T-cell responses to target tumor-associated antigens. Three signals are required for T-cell activation: (i) presentation of cognate antigen in self MHC molecules; (ii) costimulation by membrane-bound receptor-ligand pairs; and (iii) soluble factors to direct polarization of the ensuing immune response. The ability of dendritic cells (DCs) to provide all three signals required for T-cell activation makes them an ideal cancer vaccine platform. Several strategies have been developed to enhance and control antigen presentation, costimulation, and cytokine production. In this review, we discuss progress toward developing DC-based cancer vaccines by genetic modification using RNA, DNA, and recombinant viruses. Furthermore, the ability of DC-based vaccines to activate natural killer (NK) and B-cells, and the impact of gene modification strategies on these populations is described. Clinical trials using gene-modified DCs have shown modest results, therefore, further considerations for DC manipulation to enhance their clinical efficacy are also discussed.
Early Clinical Manifestations of Disseminated Sclerosis
Authors: D. K. Adams, J. M. Sutherland, W. B. Fletcher
Journal: BMJ (1950)

MBoRTSH 431 distributions of symptoms at the first examination were very similar for the two groups.The results for the patients who reported on each of the three days are shown in Table II.On each day the proportion recovering was slightly smaller in the treated than in the control series, but none of the differences is statistically significant.TABLE II.-Results for Patients who Reported on Each of Days 1, 2, and 7 Day I Day 2 Day 7 Treated Controls Treated Controls Treated Controls Cured ..