tbuckley/cabot-search huggingface dataset:
The Secretory Leukocyte Protease Inhibitor Is a Type 1 Insulin-Like Growth Factor Receptor–Regulated Protein that Protects against Liver Metastasis by Attenuating the Host Proinflammatory Response
Authors: Ni Wang, Thusanth Thuraisingam, Lucia Fallavollita, Aihao Ding, Danuta Radzioch, Pnina Brodt
Journal: Cancer Research (2006)

Abstract The secretory leukocyte protease inhibitor (SLPI) can attenuate the host proinflammatory response by blocking nuclear factor κB (NF-κB)–mediated tumor necrosis factor α (TNF-α) production in macrophages. We have previously shown that highly metastatic human and mouse carcinoma cells, on their entry into the hepatic microcirculation, trigger a rapid host proinflammatory response by inducing TNF-α production in resident Kupffer cells. Using GeneChip microarray analysis, we found that in mouse Lewis lung carcinoma subclones, SLPI expression was inversely correlated with tumor cell ability to induce a proinflammatory response and metastasize to the liver and with type 1 insulin-like growth factor receptor expression levels. To establish a causal relationship between SLPI expression and the metastatic phenotype, we generated, by transfection, multiple clones of the highly metastatic subline (H-59) that overexpress SLPI. We show here that the ability of these cells to elicit a host proinflammatory response in the liver was markedly decreased, as evidenced by reduced TNF-α production and vascular E-selectin expression, relative to controls. Moreover, these cells formed significantly fewer hepatic metastases (up to 80% reduction) as compared with mock-transfected controls. Our findings show that SLPI can decrease the liver-metastasizing potential of carcinoma cells and that this protective effect correlates with a decrease in the production of hepatic TNF-α and E-selectin. They suggest that factors that attenuate the host proinflammatory response may have a therapeutic potential in the prevention of liver metastasis. (Cancer Res 2006; 66(6): 3062-70)
Day-to-Day Changes in Coronary Hemodynamics Secondary to Constriction of Circumflex Branch of Left Coronary Artery in Conscious Dogs
Authors: ERIC C. ELLIOT, ELLIS L. JONES, COLIN M. BLOOR, ARTHUR S. LEON, DONALD E. GREGG
Journal: Circulation Research (1968)

The studies were carried out in four dogs. The effects of applying ameroid constrictors to the circumflex branch were observed on the circumflex blood flow, circumflex and peripheral circumflex pressures, circumflex reactive hyperemia and aortic-circumflex pressure difference. Recordings were successfully made for periods of 16 to 64 days. During this time the circumflex branch became completely occluded in three of the dogs. The circumflex blood flow remained in the normal range until reactive hyperemia (following a 10- to 12-second occlusion of the circumflex branch) almost disappeared; the flow then decreased to zero in 5 to 10 days. Although there was some rise in mean peripheral circumflex pressure and aortic-circumflex pressure difference before circumflex blood flow decreased, the major rise in these variables occurred only when flow and reactive hyperemia became markedly decreased. The maximum rate of rise of mean peripheral circumflex pressure varied from 6 to 15 mm Hg/24 hours. The experiments indicate that a severe degree of coronary insufficiency precedes a rise in mean peripheral circumflex pressure to 60 to 70 mm Hg. We interpret such increments in mean peripheral circumflex pressure to mean that large collaterals must be open; the studies with injection of Schlesinger mass confirmed this interpretation.
Human Solid Tumors Contain High Endothelial Venules: Association with T- and B-Lymphocyte Infiltration and Favorable Prognosis in Breast Cancer
Authors: Ludovic Martinet, Ignacio Garrido, Thomas Filleron, Sophie Le Guellec, Elisabeth Bellard, Jean-Jacques Fournie, Philippe Rochaix, Jean-Philippe Girard
Journal: Cancer Research (2011)

The mechanisms governing infiltration of lymphocytes into tumors remain poorly characterized, in spite of the critical impact of these cells on patient prognosis and therapeutic responses. High endothelial venules (HEV) are blood vessels found in lymphoid tissues, specialized in lymphocyte recruitment, but their implications in human cancer are unknown. In this article, we report the presence of MECA 79(+) blood vessels displaying all the phenotypic characteristics of HEVs in most of the 319 human primary solid tumors, including melanomas, breast, ovarian, colon, and lung carcinomas, analyzed. Tumor HEVs were specifically located within lymphocyte-rich areas, and their density within the tumor stroma was a strong predictor of infiltration by CD3(+) and CD8(+) T cells as well as B cells. Large-scale flow cytometric and quantitative reverse transcriptase-PCR analyses in freshly operated breast tumors revealed that high densities of tumor HEVs correlated with increased naive, central memory and activated effector memory T-cell infiltration and upregulation of genes related to T-helper 1 adaptive immunity and T-cell cytotoxicity. Finally, in a retrospective cohort of 146 invasive breast cancer patients, we found that high densities of tumor HEVs independently conferred a lower risk of relapse and significantly correlated with longer metastasis-free, disease-free, and overall survival rates. Together, our findings suggest that tumor HEVs function as major gateways for lymphocyte infiltration into human tumors, and may represent attractive targets for cancer diagnosis and therapy.
Application of critical pathways in the introduction of new medical technology: the intracoronary stent as a model
Authors: H.D. Aronow, K.A. Eagle, E.R. Batos, S.W. Werns, D.W.M. Muller, E. Kline-Rogers, D.J. Karavito, P.L. Russman, M. Moscucci
Journal: Journal of the American College of Cardiology (1998)
Good clinical activity and favorable toxicity profile of once weekly bortezomib, fotemustine, and dexamethasone (B‐MuD) for the treatment of relapsed multiple myeloma
Authors: Silvia Mangiacavalli, Lara Pochintesta, Cristiana Pascutto, Federica Cocito, Mario Cazzola, Alessandro Corso
Journal: American Journal of Hematology (2012)

Since multiple myeloma (MM) is still not‐curable, the management of relapse remains challenging. Given the known efficacy of alkylating agents in MM, we conducted a phase I/II study to test a new three drug combination in which Fotemustine (Muphoran), an alkylating agent of nitrosurea family, was added to bortezomib + dexamethasone backbone (B‐MuD) for the treatment of MM relapsed patients. Fotemustine was administered at two dose levels (80–100 mg/m 2 i.v.) on day 1. The original 21‐day schedule was early amended for extra‐hematological toxicity and a 35‐day schedule was adopted (Bortezomib 1.3 mg/m 2 i.v. on days 1, 8, 15, and 22, Dexamethasone 20 mg i.v. on days 1, 8, 15, and 22) for a total of six courses. Twenty‐four patients were enrolled. The maximum tolerated dose of Fotemustine was 100 mg/m 2 . The overall response rate was of 62% (CR 8%, VGPR 33%, and PR 21%). The median OS was 28.5 months, the median progression‐free survival (PFS) was 19.1 months. B‐MuD resulted effective in patients previous exposed to bortezomib without difference of response ( P = 0.25) and PFS ( P = 0.87) when compared to bortezomib‐naive patients. Thrombocytopenia was the most common AE overall. In conclusion, B‐MuD is an effective and well tolerated combination in relapsed MM patients even in advanced disease phase. © Am. J. Hematol., 88:102–106, 2013. © 2012 Wiley Periodicals, Inc.
Effects of vitamin E on cardiovascular outcomes in people with mild-to-moderate renal insufficiency: Results of the HOPE Study
Authors: Johannes F.E. Mann, Eva M. Lonn, Qilong Yi, Hertzel C. Gerstein, Byron J. Hoogwerf, Janice Pogue, Jackie Bosch, Gilles R. Dagenais, Salim Yusuf, None on behalf of the HOPE Investigators
Journal: Kidney International (2004)
Acetylcholine Receptor Antibodies in Penicillamine-lnduced Myasthenia Gravis
Authors: Tomas S. Bocanegra
Journal: JAMA (1981)

<h3>To the Editor.—</h3> The occurrence of acetylcholine receptor (AchR) antibodies in spontaneous myasthenia gravis is well recognized. These autoantibodies are also found in patients affected by penicillamineinduced myasthenia gravis, although negative or normal titers have been observed in a few patients.<sup>1,2</sup>In our recent article (1980;244:1822) we described a patient with myasthenia gravis induced by penicillamine, in whom the AchR antibody assay was normal, using denervated rat muscle as substrate. Our patient suffered a recurrence of his myasthenic symptoms eight months after discontinuance of the drug treatment. The AchR antibody assay was carried out using rat muscle and was normal again. Because of the recent demonstration that human muscle preparations may be more sensitive than rat muscle in detecting AchR antibodies,<sup>3</sup>particularly when penicillamine induced,<sup>4</sup>we repeated the test using human muscle as a source of antigen. Interestingly, the titer was 2.4 pmole/ mL (normal, ≤0.6 pmole/mL)
Enhanced Cellular Immune Responses Elicited by an Engineered HIV-1 Subtype B Consensus-based Envelope DNA Vaccine
Authors: Jian Yan, Hanna Yoon, Sanjeev Kumar, Mathura P Ramanathan, Natasha Corbitt, Michele Kutzler, Anlan Dai, Jean D Boyer, David B Weiner
Journal: Molecular Therapy (2007)

An important goal for human immunodeficiency virus (HIV) vaccines is to develop immunogens that induce broader and more potent cellular immune responses. In this study of DNA vaccine potency, we constructed a novel subtype B env gene (EY2E1-B) with the goal of increasing vaccine antigen immune potency. The vaccine cassette was designed based on subtype B-specific consensus sequence with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. The V1 and V2 loops were shortened and the cytoplasmic tail was truncated to prevent envelope recycling. Three different strains of mice (BALB/c, C57BL/6, and HLA-A2 transgenic mice) were immunized three times with pEY2E1-B or the primary DNA immunogen pEK2P-B alone. The analysis of specific antibody responses suggested that EY2E1-B could induce a moderate subtype B-specific antibody response. Moreover, this construct was up to four times more potent at driving cellular immune responses. Epitope mapping results indicated that there is an increase in the breadth and magnitude of cross-reactive cellular responses induced by the EY2E1-B immunogen. These properties suggest that such a synthetic immunogen deserves further examination for its potential to serve as a component antigen in an HIV vaccine cocktail. An important goal for human immunodeficiency virus (HIV) vaccines is to develop immunogens that induce broader and more potent cellular immune responses. In this study of DNA vaccine potency, we constructed a novel subtype B env gene (EY2E1-B) with the goal of increasing vaccine antigen immune potency. The vaccine cassette was designed based on subtype B-specific consensus sequence with several modifications, including codon optimization, RNA optimization, the addition of a Kozak sequence, and a substituted immunoglobulin E leader sequence. The V1 and V2 loops were shortened and the cytoplasmic tail was truncated to prevent envelope recycling. Three different strains of mice (BALB/c, C57BL/6, and HLA-A2 transgenic mice) were immunized three times with pEY2E1-B or the primary DNA immunogen pEK2P-B alone. The analysis of specific antibody responses suggested that EY2E1-B could induce a moderate subtype B-specific antibody response. Moreover, this construct was up to four times more potent at driving cellular immune responses. Epitope mapping results indicated that there is an increase in the breadth and magnitude of cross-reactive cellular responses induced by the EY2E1-B immunogen. These properties suggest that such a synthetic immunogen deserves further examination for its potential to serve as a component antigen in an HIV vaccine cocktail.
Effect of Chocolate on Acne Vulgaris
Authors: Lawrence Maslansky
Journal: JAMA (1970)

To the Editor.—  We should like to comment on the article, Effect of Chocolate on Acne Vulgaris, by Fulton et al (210:2071, 1969). The findings reported by this study, which disclaim the premise that chocolate aggravates acne, are similar to our conclusions in relation to the effect of chocolate.  Most physicians, including allergists, remove chocolate a priori from the patients' diets on the commonly accepted theory that chocolate may be one of the causes of their allergic symptoms, despite the fact that very little objective evidence has been accumulated.  In a preliminary study1first reported in November 1967, and also in a follow-up report in April 1969,2we revealed the results of double-blind feeding of pure defatted cocoa to allergic patients. The purpose of our study was to correlate the relationship, if any, between clinical symptoms, skin test findings, and provocative double-blind feeding tests on those patients
Dutch doctors get guidance on care of terminally ill newborn babies
Authors: T. Sheldon
Journal: BMJ (2013)

The Royal Dutch Medical Association has published professional standards to try to clarify the line between palliative care of terminally ill newborn babies and deliberately killing them.

Driving the move is the apparent failure of doctors to report cases of mercy killing of newborn babies to the government’s expert review committee of physicians, lawyers, and ethicists, to which all such cases are meant to be reported. As with the Dutch policy on euthanasia, doctors who report and adhere to guidelines will not be prosecuted.1

However, since its launch in 2006 the Central Experts Committee has received only one case involving a newborn baby. Originally up to 20 reports a year …
Palliative Surgery in Tricuspid Atresia
Authors: S. SUBRAMANIAN, IAN CARR, D. J. WATERSTON, R. E. BONHAM-CARTER
Journal: Circulation (1965)

Forty-two children diagnosed as having tricuspid atresia with diminished pulmonary blood flow are discussed. Palliative shunt surgery was done in each of these children. None of the eight infants who weighed less than 10 lb. at the time of operation survived. In 17 operations on infants who weighed between 10 and 15 lb. there were four operative and four late deaths. Glenn's operation is practicable and has been found relatively satisfactory in this group. In 21 operations on children who weighed above 15 lb. there were no operative deaths and one late death. The 17 children aged over 1 year at the time of operation are alive. In one child heart failure followed a Potts anastomosis, but regressed after Glenn's operation.
Inhibition of ultraviolet B radiation-induced interleukin 10 expression in murine keratinocytes by selenium compounds
Authors: T.S. Rafferty, C. Walker, J.A.A. Hunter, G.J. Beckett, R.C. Mckenzie
Journal: British Journal of Dermatology (2002)

Selenium is an essential trace nutrient necessary for the normal function of the immune system. Selenium compounds protect mice against ultraviolet (UV) B-induced tumours, probably by preventing oxidative damage to the host skin cells and to the host immune system. One possible mechanism of protection is that selenium can prevent oxidative stress-induced release of cytokines such as interleukin (IL)-10, which could suppress cell-mediated immunity.To determine whether selenium compounds can inhibit UVB induction of IL-10 protein in murine keratinocytes.The murine keratinocyte cell line PAM 212 was treated with or without selenomethionine (50-200 nmol L-1) or sodium selenite (1-50 nmol L(-1)) for 24 h before exposure to 200 J m(-2) UVB. The cells were stained with an antibody to IL-10, 24 h after irradiation.Preincubation with both selenium compounds inhibited UVB induction of IL-10 immunostaining, although selenomethionine was more effective. Pretreatment with 200 nmol L(-1) selenomethionine decreased IL-10 immunostaining to levels seen in the unirradiated controls.The protective effects of selenium against UVB-induced skin cancer in murine models may result, in part, from its ability to inhibit release of cytokines that are capable of suppressing cell-mediated immunity.
Anticipating Community Relationships
Authors: Merlin K. DuVal
Journal: JAMA (1965)

Our consideration of the future of medical education has properly centered on the new medical school, its relationship to its parent university, and the products we can expect it to turn out. However, I am secretly glad that we did not stop there, and that we have allowed a few additional moments to reflect on a quite different aspect which the new medical school presents, namely, the impact which it can be expected to have on the community in which it is to be located. I am learning rapidly that this is not a minor consideration, and more than once I have been tempted to suggest that the safest way to anticipate the community relationships of a new school of medicine is from the sun deck of a cruise ship in the south Pacific Ocean. However, since we can expect very little from this approach, I will try instead to
Earlier discharge for newborns may increase health risks
Authors: D. Spurgeon
Journal: BMJ (1999)

A Toronto study suggests that the trend to early discharge of newborn infants after uncomplicated vaginal delivery may not be good for the babies Drs Michael Lock and Joel Ray found that a fall in the average stay from 2.1 to 1.9 days was associated with a rise in the readmission rate of newborn infants from 5.2% to 10.4% The primary cause for readmission was neonatal jaundice.

The study was carried out among all 7009 infants …
Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers
Authors: Claudia Blattner, Jeong Hyun Lee, Kwinten Sliepen, Ronald Derking, Emilia Falkowska, Alba Torrents de la Peña, Albert Cupo, Jean-Philippe Julien, Marit van Gils, Peter S. Lee, Wenjie Peng, James C. Paulson, Pascal Poignard, Dennis R. Burton, John P. Moore, Rogier W. Sanders, Ian A. Wilson, Andrew B. Ward
Journal: Immunity (2014)
Comparison of tuberculin skin test and interferon-γ assays in patients with moderate to severe psoriasis who are candidates for antitumour necrosis factor-α therapy
Authors: N. Balato, F. Ayala, F. Gaudiello, G. Monfrecola, G. Cimmino, A. Ponticiello, M. Bocchino, A. Matarese, A. Sanduzzi
Journal: British Journal of Dermatology (2008)
High frequencies of Th1-type CD4+ T cells specific to HTLV-1 Env and Tax proteins in patients with HTLV-1–associated myelopathy/tropical spastic paraparesis
Authors: Peter K. C. Goon, Emmanuel Hanon, Tadahiko Igakura, Yuetsu Tanaka, Jonathan N. Weber, Graham P. Taylor, Charles R. M. Bangham
Journal: Blood (2002)
Lamivudine for chronic delta hepatitis
Authors: Daryl T. Lau, Edward Doo, Yoon Park, David E. Kleiner, Peter Schmid, Mary C. Kuhns, Jay H. Hoofnagle
Journal: Hepatology (1999)

Chronic delta hepatitis is a severe form of chronic liver disease caused by hepatitis delta virus (HDV) infection superimposed on chronic hepatitis B or the hepatitis B surface antigen (HBsAg) carrier state. Therapy of delta hepatitis is currently unsatisfactory. We have evaluated lamivudine (3-thiacytidine), an oral nucleoside analogue with marked effects against hepatitis B, as therapy in 5 patients with chronic hepatitis D. Five men, ages 38 to 65 years, were treated. All had HBsAg, antibody to HDV, and HDV RNA in serum, as well as persistent elevations in alanine aminotransferase (ALT) levels and liver histology showing severe chronic hepatitis with fibrosis or cirrhosis. Lamivudine was given in a dose of 100 mg orally daily for 12 months. Patients were monitored carefully and tested for HBsAg, HBV-DNA and HDV-RNA levels serially during the year of treatment and for 6 months thereafter. Liver biopsies were performed before therapy and repeated after 1 year. Serum levels of HBV DNA fell rapidly in all 5 patients, becoming undetectable even by polymerase chain reaction (PCR) in 4. However, all 5 patients remained HBsAg- and HDV-RNA–positive, and serum ALT levels and liver histology did not improve. All patients tolerated therapy well. When lamivudine was stopped, HBV-DNA levels returned to pretreatment values without a change in disease activity. Lamivudine is a potent inhibitor of HBV-DNA replication, but does not improve disease activity or lower HDV-RNA levels in patients with chronic delta hepatitis.
Quebec faces hospital closures to balance books
Authors: D. Spurgeon
Journal: BMJ (1995)

<h3>Abstract</h3> Sensitive biological markers of non-motor symptoms in Huntington’s disease (HD) are essential for the development and assessment of novel treatments. To this end we used resting state EEG to examine differences in oscillatory activity (analysing the isolated periodic as well as the complete EEG signal) and functional connectivity in 22 people with HD and 20 neurotypical controls. We then assessed the correlations between these neurophysiological markers and clinical measures of apathy and cognitive functioning. Significantly lower theta and greater delta resting state power was seen in the HD group, as well as significantly greater delta connectivity. There was a significant positive correlation between theta power and processing speed, however there were no associations between the neurophysiological and apathy measures. We speculate that these changes in oscillatory power and connectivity reflect ongoing, frontally concentrated degenerative and compensatory processes associated with HD. Our findings support the potential utility of quantitative EEG as a proximate marker for non- motor symptoms in HD.
Validated methods for assessment of subclinical atherosclerosis in rheumatology
Authors: György Kerekes, Pál Soltész, Michael T. Nurmohamed, Miguel A. Gonzalez-Gay, Maurizio Turiel, Edit Végh, Yehuda Shoenfeld, Iain McInnes, Zoltán Szekanecz
Journal: Nature Reviews Rheumatology (2012)
ACTION OF SYNTHETIC DETERGENTS ON THE METABOLISM OF BACTERIA
Authors: Zelma Baker, R. W. Harrison, Benjamin F. Miller
Journal: The Journal of Experimental Medicine (1941)

A study of the effects of synthetic detergents and wetting agents on respiration and glycolysis of Gram-positive and Gram-negative microorganisms has led to the following conclusions. 1. All the cationic detergents studied are very effective inhibitors of bacterial metabolism at 1:3000 concentration, and several are equally active at 1:30,000. Few of the anionic detergents inhibit as effectively as the cationic compounds. 2. Gram-positive and Gram-negative microorganisms are equally sensitive to the action of the cationic detergents. On the other hand, all the anionic detergents included in our studies selectively inhibit the metabolism of Gram-positive microorganisms. 3. The inhibitory action of both types of detergents is influenced markedly by hydrogen ion concentration. Cationic detergents exhibit their maximum activity in the alkaline pH range, and the anionic, in the acid range. 4. Studies of homologous series of straight chain alkyl sulfates and sulfoacetates (C(8) to C(18)) demonstrate that maximum inhibition is exerted by the 12, 14, and 16 carbon compounds (lauryl, myristyl, and cetyl). 5. It has been observed that three lauryl esters of amino acids are powerful inhibitors of bacterial metabolism. To our knowledge, the effects on bacterial metabolism of such cationic detergents (without the quaternary ammonium structure) have not been studied previously. Our results demonstrate that other cationic detergents can exhibit an inhibitory activity comparable to quaternary ammonium compounds. 6. Certain detergents stimulate bacterial metabolism at concentrations lower than the inhibiting values. This effect has been found more frequently among the anionic detergents.