tbuckley/cabot-search huggingface dataset:
Lithocholate metabolism during chemotherapy for gallstone dissolution. 2. Absorption and sulphation.
Authors: R N Allan, J L Thistle, A F Hofmann
Journal: Gut (1976)

The amount of lithocholate input and the size of the total lithocholate exchangeable pool were measured using isotope dilution in three patients ingesting chenodeoxycholic acid for gallstone dissolution and two healthy control subjects. Because the specific activity decay curve was biexponential in appearance, input was calculated using a stochastic analysis employing the Stewart-Hamilton equation. By this method, the lithocholate input and the size of the exchangeable pool in gallstone patients during chenic acid ingestion was four to five times that observed in the healthy control subjects. It was calculated that about one-fifth of the newly formed lithocholate was absorbed in both gallstone patients and healthy control subjects. The extent of sulphation of absorbed lithocholate was then measured in seven gallstone patients whto had been ingesting chenodeoxycholic acid for gallstone dissolution by defining the chemical form of radioactivity in bile after intravenous administration of labelled lithocholate. Similar studies were carried out in eight healthy control subjects, but, in addition the extent of sulphation of injected lithocholylglycine and lithocholyltaurine was also defined. When lithocholate was injected, the majority of radioactivity in bile (50-60%) was present as sulphated conjugates, both in gallstone patients and healthy control subjects. The degree of sulphation was greater for glycine than taurine conjugates, and these findings, which suggested preferential sulphation of the glycine conjugates of lithocholate, were confirmed by showing that injected lithocholylglycine was sulphated to a much greater extent than injected lithocholyltaurine. These findings indicate that in patients receiving chenic acid there is effective sulphation of lithocholate, especially its glycine conjugates, despite a considerable increase in lithocholate absorption; they may provide an explanation for the lack of hepatotoxicity of chenic acid in man.
Surface recording of His-Purkinje activity on an every-beat basis without digital averaging.
Authors: N C Flowers, V Shvartsman, B M Kennelly, G S Sohi, L G Horan
Journal: Circulation (1981)

Efforts to record evidence of electrical activity from the body surface originating in the His bundle or bundle branches have been reported since 1973. Almost exclusively, these techniques have required digital averaging of 50-100 sequential cardiac cycles. For immediate diagnostic, therapeutic and prognostic application, recording on an every-beat basis is highly desirable. This is especially important in instances of changing atrioventricular conduction, arrhythmias or less-than-constant RR intervals. Our object has been to develop a system for more nearly optimal noise reduction, to avoid the disadvantages of serial signal averaging, and to be able to record His-Purkinje activity in man on an every-beat basis. Using multiple parallel inputs wih linear amplification, additional logarithmic amplification, some bandpass filtering, and a logic circuit that ultimately examines and accepts or rejects a deflection as "true" signal, we can record, in most instances, on a beat-by-beat basis, this very valuable component of the cardiac electrical cycle.
PD08-06: ERK2 Promotes Stem Cell-Like Characteristics in Triple-Negative Breast Cancer.
Authors: C Bartholomeusz, H Saso, A Dadbin, K Kazuharu, GN Hortobagyi
Journal: Cancer Research (2011)

Abstract Background: Triple-negative breast cancer (TNBC) is resistant to targeted therapies such as hormonal therapy and HER2−targeted therapies. Thus, no specific targeted therapy is currently available for TNBC. ERK2, a component of the MAPK pathway, plays an important role in epithelial-mesenchymal transition (EMT) in MCF-7-10A, a nontransformed human mammary epithelial cell line and is required for full acquisition of stem cell-like characteristics. Inhibition of ERK2 dramatically reduces cell growth, whereas inhibition of ERK1 significantly facilitates proliferation. ERK1 mutant mice have a strikingly milder phenotype than ERK2 mutant mice, which die early in development. In addition, we have shown that the upstream target of ERK, MEK, may be a target for treating TNBC with the MEK inhibitor selumetinib. Our reverse-phase protein array analysis showed that of patients with TNBC, those with ERK2-overexpressing tumors were at higher risk of death than those with low-ERK2-expressing tumors. Therefore, we hypothesized that ERK2 promotes the tumorigenesis and metastasis of TNBC. We sought to determine the role of ERK2 in the tumorigenic and metastatic activities in TNBC and whether ERK2 is required for acquisition of stem cell-like characteristics in TNBC. Methods: We studied the role of ERK1 and ERK2 in the TNBC cell line SUM-149. We used shRNA to specifically knockdown ERK1 and ERK2 (shERK1 and shERK2) and examined whether knocking down ERK1 and ERK2 correlated with EMT regulation, migration, and tumorigenicity in TNBC cells. Results: Compared with parental SUM-149 cells, stable clones that constitutively expressed shERK1 or shERK2 showed no difference in growth rate. However, knocking down ERK2 significantly inhibited migration and the acquisition of stem cell-like characteristics (CD44+/CD24-) in SUM-149 cells in vitro. In addition, knockdown of ERK2 also inhibited anchorage-independent growth, an indicator of in vivo tumorigenicity, whereas knockdown of ERK1 did not inhibit anchorage-independent growth. However, inhibition of ERK1 or ERK2 in 2D or 3D cell culture did not correlate with changes in epithelial and mesenchymal markers by western blot analysis. Conclusion: Our data demonstrate that ERK2 may promote the tumorigenesis of TNBC via enriching cancer stem cells. Our long-term goal is to develop ERK-targeted therapy for TNBC. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD08-06.
rational health care should be offered to all persons: rich or poor, well or sick
Authors: Paul S Frame
Journal: BMJ (2005)

Iona Heath makes the provocative assertion that shifting spending from preventive medicine for well populations in developed countries to disease treatments for sick people in poor countries will benefit the health of everyone.

Heath admits that people in developed countries live longer and are, by objective measures, healthier. But she asserts that they suffer from greater rates of self-reported illness created by a medical, industrial, and political conspiracy to medicalize trivial problems in healthy persons. Thus they are somehow less healthy than their brethren in the underdeveloped world, even though they have a significantly longer life span. She proposes to share some of the excess spent in developed countries with the poor in underdeveloped countries, perhaps so they can share in the misery of increased awareness of and rates of self-reported illness? Along the way, one hopes that they will …
Exposing the abuse of Chinese orphans
Authors: P. Kandela
Journal: BMJ (1996)

In January, Human Rights Watch/Asia published evidence of horrific maltreatment of children in the Shanghai Children's Welfare Institute.1 The publicity led to widespread public indignation in the West and calls for pressure to be put on the Chinese government to improve conditions for such children. This exposure was the result of the efforts of a Chinese physician, Dr Zhang Shuyun, who assembled evidence from firsthand experience, and then escaped to bring the matter to world attention. Dr Zhang is currently in the United Kingdom and agreed to be interviewed to give a firsthand account of her work in the orphanage and her subsequent decision to leave China and expose the abuses she had observed.

I met Dr Zhang while she was staying with friends in London. She was friendly and relaxed as she told me, through an interpreter, about her life in Shanghai and how she came to publicise the maltreatment of orphaned and disabled children.

Dr Zhang was born in Shanghai in 1942 and grew up there. She studied medicine at the Beijing University School of Medical Sciences and since then her main specialty has been paediatrics, including research on aspects of hygiene. She also undertook research on people suffering from chronic lung disease, especially those working in the shipbuilding industry and exposed to asbestos.

“I was anxious to go back and work again with children,” Dr Zhang told me. This ambition was realised in 1988 when she joined the Shanghai Children's Welfare Institute as a senior medical officer. This institution was originally founded by Catholic missionaries in 1912 and was maintained as a home for orphaned and abandoned children when the Communists came to power. In 1988 the government built a seven storey modern institute in the grounds of the …
Ban the Sunset? Nonpropositional Content and Regulation of Pharmaceutical Advertising
Authors: Paul Biegler, Patrick Vargas
Journal: The American Journal of Bioethics (2013)

The risk that direct-to-consumer advertising of prescription pharmaceuticals (DTCA) may increase inappropriate medicine use is well recognized. The U.S. Food and Drug Administration addresses this concern by subjecting DTCA content to strict scrutiny. Its strictures are, however, heavily focused on the explicit claims made in commercials, what we term their "propositional content." Yet research in social psychology suggests advertising employs techniques to influence viewers via nonpropositional content, for example, images and music. We argue that one such technique, evaluative conditioning, is operative in DTCA. We further argue that evaluative conditioning fosters unjustified beliefs about drug safety and efficacy, antagonising the autonomy of viewers' choices about advertised medicines. We conclude that current guidelines are deficient in failing to account for evaluative conditioning, and that more research and debate are needed to determine the permissibility of this and other forms of nonpropositional persuasion.
Pneumococcus Arthritis with Notes of Seven Cases
Authors: N. Raw
Journal: BMJ (1901)

PNEUMOCOCCUS ARTHRITIS.[samaek 1803 with these organisms in their nasal or aural discharge are capable of giving rise to diphtheria in others.On the other hand, it may be argued that diphtheria bacilli, as with other organisms, may be virulent to man and not to animals and vice ver8d, so that these i cases, which after all are in the majority, may have been virulent in their original state.No. 20, though proved to be a virulent Klebs-Loeffier bacil- lus, gave no growth or acidity in sugar broth, which suggests that this test, on which so much stress has been laid by some writers, is not infallible.CONCLUSIONS.
Mild Hyperlactatemia in Stable Septic Patients Is Due to Impaired Lactate Clearance Rather Than Overproduction
Authors: JACQUES LEVRAUT, JEAN-PIERRE CIEBIERA, STEPHANE CHAVE, OLIVIER RABARY, PATRICK JAMBOU, MICHEL CARLES, DOMINIQUE GRIMAUD
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

A prospective study was conducted on 34 stable septic patients to determine whether mild hyperlactatemia is a marker of lactate overproduction or an indicator of lactate underutilization during sepsis. Plasma lactate clearance and lactate production were evaluated by modeling the lactate kinetic induced by an infusion of 1 mmol/kg l-lactate over 15 min. The patients were divided in two groups depending on their blood lactate: ⩽ 1.5 mmol/L (n = 20, lactate = 1.2 ± 0.2 mmol/L) or ⩾ 2 mmol/L (n = 10, lactate = 2.6 ± 0.6 mmol/L). The hyperlactatemic patients had a lower lactate clearance (473 ± 102 ml/kg/h) than those with normal blood lactate (1,002 ± 284 ml/kg/h, p < 0.001), whereas lactate production in the two groups was similar (1,194 ± 230 and 1,181 ± 325 μ mol/kg/h, p = 0.90). A second analysis including all the patients confirmed that the blood lactate concentration was closely linked to the reciprocal of lactate clearance (r2 = 0.73, p < 0.001) but not to lactate production (r2 = 0.03, p = 0.29). We conclude that a mild hyperlactatemia occurring in a stable septic patient is mainly due to a defect in lactate utilization.
Abstract 3348: Inhibition of MDMX by XI-011 induces p53-mediated apoptosis in head and neck cancer.
Authors: In Sun Ryu, Chang Hwan Ryu, Hyun Bae Park, Eunhye Kim, Jong-Lyel Roh
Journal: Cancer Research (2013)

Abstract Overexpression of MDM2 or MDMX inactivates the tumor-suppressive function of p53. Restoration of p53 function counteracting these p53 repressors can lead to in vivo tumor regression. Therefore, we evaluated whether the restoration of p53 function by a small-molecule p53 activator XI-011, a pseudouria derivative NSC146109, induce apoptosis in head-and-neck cancer (HNC). The effects of XI-011 treatment in four HNC cell lines were tested, individually or in combination with nutlin-3a, an inhibitor of MDM2-p53 interactions, and its growth suppression, cell-cycle arrest, and apoptosis were assessed. XI-011 induced accumulation and reactivation of p53 in a wild-type TP53-bearing HNC cell line. XI-011 showed maximal growth suppression in tumor cells with overexpression of MDMX and MDMX-dependent p53 degradation. With down-regulation of MDMX mRNA and protein levels, XI-011 upregulated expression of p21 and proapoptotic genes and promoted apoptosis in a dose-dependent manner. Notably, the apoptotic response was blocked by inhibition of p53 or MDMX gene expression, demonstrating the p53 and MDMX dependence of XI-011 effects. XI-011 decreased the viability of HNC cells expression low levels of MDMX in a less-efficient manner. Interestingly, in combination therapy, XI-011 synergistically acted with nutlin-3a to inhibit growth of HNC cells. Our data suggest that the MDMX inhibition and p53 functional restoration by XI-011 effectively induced cytotoxicity and apoptosis in cancer cells, an action that may offer a promising strategy for treating HNC. Citation Format: In Sun Ryu, Chang Hwan Ryu, Hyun Bae Park, Eunhye Kim, Jong-Lyel Roh. Inhibition of MDMX by XI-011 induces p53-mediated apoptosis in head and neck cancer. [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 3348. doi:10.1158/1538-7445.AM2013-3348
Effects of ONO-1078, a peptide leukotriene antagonist, on endotoxin-induced acute lung injury.
Authors: A Ishizaka, N Hasegawa, F Sakamaki, S Tasaka, H Nakamura, K Kishikawa, A Yamada, T Obata, K Sayama, T Urano
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS group (n = 9) injected intravenously with 2 mg E. coli LPS, an ONO group (n = 8) receiving 30 mg/kg of intraperitoneal ONO, and an LPS+ONO group (n = 6) receiving 30 mg/kg of ONO intraperitoneally 10 min before the LPS injection. The [125I]albumin lung plasma ratio, which is a parameter of acute lung injury, was significantly increased (p < 0.01) in the LPS group compared with the saline, ONO, and LPS+ONO groups. The [125I]albumin BAL fluid plasma ratio was also increased (p < 0.01) in the LPS group compared with the other groups. ONO pretreatment attenuated the LPS-induced increases in neutrophil counts in the BAL fluid. In vitro studies showed that ONO suppresses the neutrophil chemotaxis induced by LTB4, zymosan-activated serum, and FMLP. We conclude that (1) ONO-1078 attenuates LPS-induced acute lung injury; and (2) this effect appears mainly a result of its potent antagonistic actions against peptide leukotrienes and also, in part, the suppression of neutrophil chemotaxis.
Genome-wide scan identifies variant in 2q12.3 associated with risk for multiple myeloma
Authors: Stephen W. Erickson, Vinay R. Raj, Owen W. Stephens, Ishwori Dhakal, Shweta S. Chavan, Naveen Sanathkumar, Elizabeth Ann Coleman, Jeannette Y. Lee, Julia A. Goodwin, Senu Apewokin, Daohong Zhou, Joshua Epstein, Christoph J. Heuck, Annette J. Vangsted
Journal: Blood (2014)
Detection of hepatitis C virus replication in ovarian metastases of a patient with hepatocellular carcinoma
Authors: Wulf O. Böcher, Hanns-F. Löhr, Kurt W. Steegmüller, Stephan Störkel, Ursula Jäger, Karl-H. Meyer zum Büschenfelde, Guido Gerken
Journal: Journal of Hepatology (1994)
Research Advances in Pemphigus
Authors: Grant James Anhalt, Luis A. Diaz
Journal: JAMA (2001)

Pemphigus is an autoimmune disorder, known to be caused by autoantibodies directed against critical adhesion molecules of squamous epithelial cells, the desmogleins. These autoantibodies induce blistering of skin and mucosal surfaces and lead to severe morbidity and, potentially, death. Key factors include associated major histocompatibility complex class II genes, the structure of the desmoglein antigens, and the role of autoantibody in impairing cellular adhesion. This article discusses the precise structure of the major histocompatibility complex class II gene-peptide-T-cell receptor complex involved and of the environmental and genetic factors that induce autoimmunity against desmoglein 1. Discovery of antigen-specific immunotherapy and insight into environmental factors that initiate autoimmunity in genetically susceptible individuals are needed.
The influence of four dual-cure resin cements and surface treatment selection to bond strength of fiber post
Authors: Chang Liu, Hong Liu, Yue-Tong Qian, Song Zhu, Su-Qian Zhao
Journal: International Journal of Oral Science (2013)

In this study, we evaluate the influence of post surface pre-treatments on the bond strength of four different cements to glass fiber posts. Eighty extracted human maxillary central incisors and canines were endodontically treated and standardized post spaces were prepared. Four post pre-treatments were tested: (i) no pre-treatment (NS, control), (ii) sandblasting (SA), (iii) silanization (SI) and (iv) sandblasting followed by silanization (SS). Per pre-treatment, four dual-cure resin cements were used for luting posts: DMG LUXACORE Smartmix Dual, Multilink Automix, RelyX Unicem and Panavia F2.0. All the specimens were subjected to micro push-out test. Two-way analysis of variance and Tukey post hoc tests were performed (α=0.05) to analyze the data. Bond strength was significantly affected by the type of resin cement, and bond strengths of RelyX Unicem and Panavia F2.0 to the fiber posts were significantly higher than the other cement groups. Sandblasting significantly increased the bond strength of DMG group to the fiber posts. Sandblasting of glass fiber posts could enhance resin cement adhesion during tooth restoration, as scientists in China suggest. During endodontic treatment, such as root canal surgery, teeth must be hollowed out and rebuilt. Glass fiber posts and resin cements can replace lost structural support, but weak bonding between them can lead to restoration failure. In a study using human teeth, Chang Liu and co-workers at Jilin University in China analyzed the bonding of four different resin cements under different conditions. The type of resin cement significantly affected bonding to the posts regardless of pre-treatment, with two cements outperforming the others. However, one type of cement, called DMG Luxacore, adhered far better to the post following small-scale sandblasting. The sandblasting roughens the glass surface, increasing both the bonding area and interlocking between post and cement.
Abstract 1006: Structural peculiarities of flavonoids influence anti-angiogenic, cytotoxic and antioxidant effects: experimental and insilico analysis
Authors: Raju N. Gacche, Harshala D. Shegokar, Dhananjay S. Gond, Rohan J. Meshram
Journal: Cancer Research (2014)

Abstract Structural diversity of flavonoids and biological activities has remained an important discourse in the mainstream of flavonoid research. In the present studies different class of flavonoids such as flavones, flavanones and flavanolols were evaluated for their antiangiogenic, cytotoxic and antioxidant activities. The anti-angiogenic activity was evaluated using in vivo chorioallantoic membrane model (CAM), antioxidant potential and kinetics of free radical scavenging activity was determined using DPPH (2, 2-diphenyl-1-picryl hydrazine) and superoxide anion radical (SOR) scavenging assays, while cytotoxicity against selected cancer cell lines was carried out using MTT cell viability assay. The physicochemical properties/quantum chemical discriptors of the selected flavonoids were calculated using BioMed CAChe 6.1.10 drug. The selected flavonoids were docked in silico onto the proangiogenic peptides such as vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF-1α), and vascular endothelial growth factor receptor-2 (VEGFR2) and others from human origin. The results of the present investigation are discussed in the mainstream of structure activity relationship which may be useful in translating flavonoids as therapeutic molecules targeting angiogenesis. References 1. Gacche R. N. Shegokar Harshala, Gond Dhananjay , A. D. Jadhav and Ghole Vikram. (2010). Effect of Hydroxyl Substitution of Flavone on Antiangiogenic and Free Radical Scavenging Activities: A Structure Activity Relationship Studies Using Computational Tools. European J. Pharmaceutical Science 39, 37-44. 2. Gacche R. N. Shegokar Harshala, Gond Dhananjay , Zhenzhou Yang, A. D. Jadhav (2011). Evaluation of selected flavonoids as antiangiogenic, anticancer and radical scavenging agents: an experimental and in silico analysis. Cell Biochemistry and Biophysics 61, 651-663. DOI 10.1007/s12013-011-9252-z. 3. Gacche RN and Meshram RJ (2013) Targeting Tumor Micro-environment for Design and Development of Novel Anti-angiogenic Agents Arresting Tumor Growth. Progress in Biophysics &amp; Molecular Biology 113 (2013) 333-354. Note: This abstract was not presented at the meeting. Citation Format: Raju N. Gacche, Harshala D. Shegokar, Dhananjay S. Gond, Rohan J. Meshram. Structural peculiarities of flavonoids influence anti-angiogenic, cytotoxic and antioxidant effects: experimental and insilico analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1006. doi:10.1158/1538-7445.AM2014-1006
Experts urge vaccination to try to control cholera outbreak in Haiti
Authors: J. Zarocostas
Journal: BMJ (2011)

Experts have called for a pilot project to test whether the cholera vaccine might help to contain Haiti’s ongoing outbreak of the disease. They are also urging the creation of an international stockpile of cholera vaccine for future outbreaks.

Roger Glass, director of the Fogarty International Center for Advanced Study in the Health Sciences at the US National Institutes of Health (NIH) and associate director for international research at the NIH, said, “In the short term we should make use of the limited amount of vaccine we have.

“In the long term we need to make sure we have adequate supplies to respond to …