tbuckley/cabot-search huggingface dataset:
Generation of a Flexible Cell Line with Regulatable, High-Level Expression of HIV Gag/Pol Particles Capable of Packaging HIV-Derived Vectors
Authors: Sandra Sparacio, Tanya Pfeiffer, Heiner Schaal, Valerie Bosch
Journal: Molecular Therapy (2001)

HIV-derived vectors are of potential clinical relevance due to their ability to transduce nondividing cells in vitro and in vivo. However, the generation of cell lines stably and reproducibly expressing high amounts of defined subviral particles, capable of packaging and transducing HIV-derived vectors, has been hampered by the cytotoxicity of some of the required gene products, in particular of the HIV-1 protease. The successful use of regulatable gene expression systems to overcome this problem requires that the remaining basally expressed gene product activity is below the threshold for cytotoxicity. To try to achieve this, we have consecutively introduced appropriate plasmids, encoding HIV rev and HIV gag/pol gene products, each under the control of separate ecdysone-inducible promoters, into human 293 cells. Using a protocol in which a specific HIV protease inhibitor, Saquinavir, was continuously present in the culture medium during selection, we could generate stable cell lines inducibly expressing high amounts of subviral particles. A cell line, termed 293-Rev/Gag/Pol(i), which has been characterized in more detail, inducibly releases, within 48 h postinduction, high amounts of HIV Gag/Pol particles (about 10 microg CA/ml). These HIV Gag/Pol particles can package and transduce third-generation HIV vectors to high titers. Thus, in addition to other applications, the 293-Rev/Gag/Pol(i) cell line represents a "founder" packaging cell line which, depending on the requirement, can be further modified to include specific transgene-encoding vector and targeting glycoprotein genes.
Firearm Violence and Public Health
Authors: Eric S. H. Ching
Journal: JAMA (1994)

To the Editor.  —The Commentary by the New York Academy of Medicine panel1is seriously flawed as public health policy and yet another example of the fact that a medical degree does not a criminologist or policy analyst make.  The article completely ignored the vast criminological research literature on the subject, which generally concludes that the gun control measures proposed by the panel have failed and, even worse, may actually have led to more innocent victims.2  Rational public policy balances benefits and costs. In ignoring or dismissing the extensive criminological literature on the subject, the panel failed to explicitly consider the benefits conferred by private firearms ownership, which are potentially large. For example, research during the past decade suggests that between 30 and 75 lives may be saved with privately owned guns for each life taken with one.3,4Instead, the panel's one-sided costs only approach to firearms
REACTIVE LYSIS: THE COMPLEMENT-MEDIATED LYSIS OF UNSENSITIZED CELLS
Authors: P. J. Lachmann, R. A. Thompson
Journal: The Journal of Experimental Medicine (1970)

It has been shown that the "activated reactor" that is produced in certain human sera by complement activation is a stable complex of the fifth and sixth component of complement (C56). On interaction with C7, the indicator factor, a complex C567 is formed which for a short time (half-life less than 1 min) has an activated binding site and can attach itself to normal red cell membranes, conferring on them the hemolytic properties of the "heat stable" complement intermediate EC 1 approximately 7, the capacity to be lysed by C8 and C9. These cells have neither antibody nor the complement components up to C3 bound on them. The binding site-activated C567c-can similarly bind to other hydrophobic surfaces, including agarose gel where it forms a "stainable line". If the complex is not bound to a surface, the binding site decays and the resulting complex will no longer give rise to lysis. However it will still inactivate C8 and C9 in solution. The sera that can generate activated reactor apparently do so because they have an excess of C5 and C6, compared to their content of C7. The phenomenon of reactive lysis thus represents complement-mediated lysis of unsensitized cells initiated at the C5 stage by a stable complex (C56) which was generated by complement activation at a distance. The immunochemistry of the phenomenon is described and some of its implications discussed.
Typhoid Fever Complicated by Hepatitis, Nephritis, and Thrombocytopenia
Authors: Daniel Faierman
Journal: JAMA (1972)

A patient with documented typhoid fever manifested several very severe and unusual complications. These included (1) typhoid hepatitis characterized histologically by "Mallory nodules" and clinically by profound jaundice and hepatic encephalopathy, (2) acute renal failure with histological findings suggestive of typhoid nephritis, and (3) symptomatic thrombocytopenia. Typhoid as a cause of acute pyrexial disorders remains an important entity in the United States.
Judge rules that government must disclose figures on late abortions
Authors: C. Dyer
Journal: BMJ (2011)

The UK government has lost a High Court battle to keep secret “sensitive” statistics on late abortions, which it argued could lead to the identification of patients and doctors.

The small numbers who had late abortions for certain conditions meant that individual patients could have their identities revealed with potentially “awful consequences,” the Department of Health argued.

But at the high court in London, Mr Justice Cranston upheld a ruling by the information tribunal in October 2009 that freedom of information rules required the statistics on late abortions to be disclosed. The ruling followed a freedom …
Weight watching in cardiology: low molecular weight heparin for acute coronary syndromes
Authors: Marcel Levi, Ron J.G. Peters, Harry R. Büller
Journal: Cardiovascular Research (1998)

Heparin is available for clinical use since the 1950's and has over the last years firmly established its role as the anticoagulant agent of choice in the prevention and treatment of venous thromboembolism as well as in the management of acute coronary syndromes [1]. Heparin anticoagulation, however, has limitations, partly due to the unpredictable bioavailability of the compound and its large inter- and intraindividual biological effect, requiring continuous intravenous infusion, frequent monitoring of anticoagulation and dose adjustments. Furthermore, the present anticoagulant treatment of patients in a number of clinical situations, such as unstable angina, is still associated with unsatisfactory efficacy and safety in a substantial number of patients.

Recently, low molecular weight heparins (LMWH's), consisting of low molecular weight fragments of depolymerized heparin, have been introduced [2]. In laboratory studies it was shown that LMWH's have a relatively high anti-factor Xa to anti-factor IIa ratio, which was thought to be beneficial in terms of a better anticoagulant while less hemorraghic potential. Moreover, LMWH's were shown to have a near complete bioavailability and a much more predictable pharmacokinetic and pharmacodynamic effect, rendering frequent laboratory monitoring redundant and enabling fixed dosing based on bodyweight via the subcutaneous route.

In clinical studies on the prevention and treatment of venous thromboembolism LMWH's showed at least equal and in some cases superior efficacy and safety as compared to unfractionated heparin [3, 4]. The relatively easy administration of LMWH by once or twice daily subcutaneous administrations has even enabled the home treatment of a large number … 

* Corresponding author: Tel.: +31 (20) 5669111; fax: +31 (20) 6968833; E-mail m.m.levi@amc.uva.nl
Efficacy of etanercept for treatment of Crohn's related spondyloarthritis but not colitis
Authors: H Marzo-Ortega
Journal: Annals of the Rheumatic Diseases (2002)

The seronegative spondyloarthropathies (SpAs) are associated both with clinical and subclinical colitis. Recently biological blockade with the tumour necrosis factor alpha (TNFα) antagonists infliximab and etanercept has been shown to be effective in the treatment of SpA. However, only infliximab is efficacious in the treatment of colitis in patients with Crohn's SpA. We report on two patients with SpA and associated Crohn's disease treated with etanercept whose arthritis showed an excellent response with complete resolution of spinal pathology, whereas their Crohn's disease persisted or flared. These findings suggest that the effect of TNFα blockade in SpA differs between the joint and the bowel.
Missed opportunity to advance debate on assisted dying
Authors: J. L. Bernheim
Journal: BMJ (2011)

In his review of Terry Pratchett’s documentary on assisted dying O’Neill focused on caregivers’ feelings.1 From experience, I can confirm that caregivers and loved ones often try to dissuade patients from euthanasia. However, I submit that caregivers’ feelings are a secondary concern because patients’ feelings should count for more than caregivers’. As for families, evidence from the Netherlands is reassuring: on average, bereavements …
6-Mercaptopurine metabolism in Crohn's disease: correlation with efficacy and toxicity.
Authors: C Cuffari, Y Theoret, S Latour, G Seidman
Journal: Gut (1996)

BACKGROUND: 6-Mercaptopurine (6-MP) has confirmed short and longterm efficacy in the treatment of IBD. However, the relation between its metabolism, efficacy, and side effects is not well understood. AIMS: To assay 6-MP metabolites and to correlate levels with drug compliance, disease activity, and adverse effects of treatment. PATIENTS: Heparinised blood was obtained prior to daily administration of 6-MP in 25 adolescent Crohn9s disease patients (14 ileocolitis, 11 colitis) receiving 1.2 (range 0.4-1.6) mg/kg/day for a mean of 17 (range 4-65) months. METHODS: Erythrocyte free bases 6-thioguanine (6-TG) and 6-methyl-mercaptopurine (6-MMP) were measured (pmol/8 x 10(8) red blood cells) using reverse phase high performance liquid chromatography. RESULTS: Disease activity (modified Harvey-Bradshaw index) improved significantly with 6-MP (p = 0.001). Clinical remission was achieved in 72% of patients, who stopped taking prednisone, or were successfully weaned to a low alternate day dose (&lt; 0.4 mg/kg/OD). Remission correlated well with erythrocyte 6-TG (p &lt; 0.05), but not 6-MMP levels. Neutropenia was associated with 6-MP use (p &lt; 0.005), but did not correlate with erythrocyte 6-MP metabolite levels. One patient refractory to 6-MP had 6-TG, but no measureable 6-MMP production, suggesting deficient thiopurine methyl-transferase activity or poor compliance. 6-MP induced complications (hepatitis, pancreatitis, and marrow suppression) were generally associated with increased 6-MMP levels. CONCLUSIONS: These results suggest that high performance liquid chromatography measurement of erythrocyte 6-MP metabolites may provide a quantitative assessment of patient responsiveness and compliance to treatment. The data support an immunosuppressive role for 6-TG, and potential cytotoxicity of raised 6-MMP levels.
TCT-881 Embolic Cerebral Insults and Microbleeds after Percutaneous Aortic Valve Replacement and Surgical Aortic Valve Replacement detected by Magnetic Resonance Imaging
Authors: Stephan Ensminger, Sabine Ott, Stephan Achenbach, Christian Heim, Richard Feyrer, Sabrina Loders, Arndt Doerfler, Werner Daniel, Michael Weyand, Josef Ludwig, Martin Arnold
Journal: Journal of the American College of Cardiology (2012)
Health Effects of Naturally Radioactive Water Ingestion: The Need for Enhanced Studies
Authors: Irina Guseva Canu, Olivier Laurent, Nathalie Pires, Dominique Laurier, Isabelle Dublineau
Journal: Environmental Health Perspectives (2011)

Background: Radiological pollution is a potentially important aspect of water quality. However, relatively few studies have been conducted to document its possible health effects.Objective: In this commentary we discuss available epidemiological findings and related data from experimental studies concerning the health effects of naturally radioactive water ingestion.Discussion: Despite modest epidemiological evidence of uranium nephrotoxicity and radium effects on bone, available data are not sufficient to quantify the health effects of naturally occurring radionuclides in water. Methodological limitations (exposure measurement methods, control for confounding, sample size) affect most studies. Power calculations should be conducted before launching new epidemiological studies focusing on late pathological outcomes. Studies based on biomarkers of exposure and adverse effects may be helpful but should involve more specific molecules than biomarkers used in previous studies. Experimental data on ingestion of drinking water are limited to uranium studies, and there is some disagreement between these studies about the nephrotoxicity threshold.Conclusion: Further experimental and enhanced epidemiological studies should help to reduce uncertainties resulting from dose estimation to dose–response characterization.
Intermittent Fasts-Reply
Authors: Garfield G. Duncan
Journal: JAMA (1963)

<h3>To the Editor:—</h3> By comparing Benedict's adult male subject weighing 130 lb (59 kg) with those that are very obese, Dr. Wishnofsky introduces features which may be misleading. It is safe to assume that a thin person without appreciable amounts of available endogenous fat would suffer greater loss of protein than an obese subject whose reserves of fat are depleted during the complete fast. If this is the case, the obese subject may lose considerably less nitrogen than the thin patient. Studies to date have shown this to be so. Losses of weight from 4 to 8 lb (1.8 to 3.6 kg) in 24 hours in the early days of the fast are not rare. These instances, we realize, are exaggerated illustrations of the water and sodium diuresis which is usual during the first day or two of the fast. Such a great loss in such a short period is
Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis
Authors: Aurélien Trompette, Eva S Gollwitzer, Koshika Yadava, Anke K Sichelstiel, Norbert Sprenger, Catherine Ngom-Bru, Carine Blanchard, Tobias Junt, Laurent P Nicod, Nicola L Harris, Benjamin J Marsland
Journal: Nature Medicine (2014)
Stable Suppression of Tumorigenicity by Pin1-Targeted RNA Interference in Prostate Cancer
Authors: Akihide Ryo, Hiroji Uemura, Hitoshi Ishiguro, Tatsuya Saitoh, Akira Yamaguchi, Kilian Perrem, Yoshinobu Kubota, Kun Ping Lu, Ichiro Aoki
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The peptidyl-prolyl isomrase Pin1 plays a catalytic role in oncogenesis in solid cancers, including prostate cancer. In the present study, we sought to determine the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in prostate cancer. Experimental Design: A retrovirus-mediated RNA interference targeting Pin1 was expressed in PC3 and LNCaP cells, and cell growth and several transformed properties were investigated. Results: The stable expression of Pin1-specific small interfering RNA constructs in PC3 and LNCaP cells significantly reduced cellular proliferation, colony formation, migration, and invasion but strongly enhanced the apoptotic response induced by serum depletion or treatment with anticancer agents. Furthermore, Pin1 depletion significantly suppressed tumorigenic potential in athymic mice, resulting in the inhibition of both tumor growth and angiogeneisis. Conclusions: These results strongly suggest that Pin1 plays an important role not only in tumorigenesis but also in the maintenance of the transformed phenotype in prostate cancer cells. Hence, Pin1 may serve as a promising therapeutic target, particularly for recurrent prostate tumors.
Absence of 12/15-Lipoxygenase Expression Decreases Lipid Peroxidation and Atherogenesis in Apolipoprotein E–Deficient Mice
Authors: Tillmann Cyrus, Domenico Praticò, Lei Zhao, Joseph L. Witztum, Daniel J. Rader, Joshua Rokach, Garret A. FitzGerald, Colin D. Funk
Journal: Circulation (2001)

Background —The enzyme 12/15-lipoxygenase (12/15-LO) has been implicated in the oxidative modification of LDL. In a murine model, we tested the hypothesis that deletion of 12/15-LO decreases atherogenesis by reducing oxidant stress, as measured by 2 indices of lipid peroxidation: isoprostane generation and autoantibody formation to malondialdehyde (MDA)-LDL, an epitope of LDL formed as a result of oxidative modification. Methods and Results —12/15-LO–deficient (12/15-LO −/− ) mice were crossed with apolipoprotein E–deficient (apoE −/− ) mice. At 10 weeks of age, atherosclerotic lesion initiation was significantly delayed in the double-knockout mice. The rate of lesion progression was diminished at 8 and 12 months, and even at 15 months, lesion size was reduced 50% ( P &lt;0.0005) compared with control apoE −/− mice. The urinary and plasma levels of the specific isoprostane 8,12-iso-iPF 2α -VI, as well as IgG autoantibodies against MDA-LDL, were significantly reduced in the double-deficient mice in parallel with decreased atherosclerosis at all time points from 10 weeks to 15 months of age compared with apoE −/− controls. Conclusions —Enzymatic action of 12/15-LO contributes significantly to atherosclerotic lesion initiation and propagation in this murine model. Strong positive correlations exist between lesion size, isoprostane levels, and MDA-LDL autoantibodies, providing in vivo evidence for an enzymatic (12/15-LO) component to lipid peroxidation and atherogenesis.
Medicine and Society in Wakefield and Huddersfield, 1780-1870
Authors: W. F. Bynum
Journal: JAMA (1988)

Reading almost 400 pages of text and more than 100 pages of appendices, notes, and bibliography about 90 years of medicine in Wakefield and Huddersfield might remind one of the story of the little girl who read a massive volume on penguins. Asked if she enjoyed it, she replied, "It was a very good book, but it told me more about penguins than I wanted to know." Even British readers might relate to Wakefield primarily as the place where Oliver Goldsmith's vicar lived and to Huddersfield as a community with a struggling, lower-division soccer team. What will Americans make of it? It has been said that Hilary Marland's book is unlikely to appeal to the casual reader, but it is nonetheless important for all that. Her aim is to provide a comprehensive account of health care, medical institutions, and the medical profession in these two Yorkshire communities about 10 miles
Association of Hemoglobin Levels With Clinical Outcomes in Acute Coronary Syndromes
Authors: Marc S. Sabatine, David A. Morrow, Robert P. Giugliano, Paul B.J. Burton, Sabina A. Murphy, Carolyn H. McCabe, C. Michael Gibson, Eugene Braunwald
Journal: Circulation (2005)

Background— In the setting of an acute coronary syndrome (ACS), anemia has the potential to worsen myocardial ischemia; however, data relating anemia to clinical outcomes in ACS remain limited. Methods and Results— We examined the association between baseline hemoglobin values and major adverse cardiovascular events through 30 days in 39 922 patients enrolled in clinical trials of ACS. After adjustment for differences in baseline characteristics and index hospitalization treatments, a reverse J-shaped relationship between baseline hemoglobin values and major adverse cardiovascular events was observed. In patients with ST-elevation myocardial infarction, when those with hemoglobin values between 14 and 15 g/dL were used as the reference, cardiovascular mortality increased as hemoglobin levels fell below 14 g/dL, with an adjusted OR of 1.21 (95% CI 1.12 to 1.30, P &lt;0.001) for each 1-g/dL decrement in hemoglobin. At the other end of the range of hemoglobin, patients with hemoglobin values &gt;17 g/dL also had excess mortality (OR 1.79, 95% CI 1.18 to 2.71, P =0.007). In patients with non–ST-elevation ACS, with those with hemoglobin 15 to 16 g/dL used as the reference, the likelihood of cardiovascular death, myocardial infarction, or recurrent ischemia increased as the hemoglobin fell below 11 g/dL, with an adjusted OR of 1.45 (95% CI 1.33 to 1.58, P &lt;0.001) for each 1 g/dL decrement in hemoglobin. Patients with hemoglobin values &gt;16 g/dL also had an increased rate of death or ischemic events (OR 1.31, 95% CI 1.03 to 1.66, P =0.027). Conclusions— Anemia is a powerful and independent predictor of major adverse cardiovascular events in patients across the spectrum of ACS.
CATAPHORIC TREATMENT OF CANCER.
Authors: G. BETTON MASSEY
Journal: JAMA (1899)

The insertion of nascent salts of mercury within the human body by electric diffusion in a strength that will deluge a given tract of tissue or a growth with these germicides without materially affecting the remainder of the body constitutes a novel therapeutic procedure which the writer contributed to medical science as a cure for cancer, in a paper before this Section of theAssociationat its Philadelphia meeting, in 1897. Further experience with this method in primary cancers and local recurrences in accessible situations has demonstrated an even greater usefulness than was anticipated, as the technic has improved and greater currents have been used. The importance of this method of destroying germs within the body would be sufficiently great if its applicability to the cure of local cancerous foci is alone considered, for cancerous affections are increasing rapidly in frequency throughout the country, but an examination of the method
A novel point mutation in the gene encoding capillary morphogenesis protein 2 in a Japanese patient with juvenile hyaline fibromatosis
Authors: A. Hatamochi, T. Sasaki, T. Kawaguchi, H. Suzuki, S. Yamazaki
Journal: British Journal of Dermatology (2007)

Journal Article A novel point mutation in the gene encoding capillary morphogenesis protein 2 in a Japanese patient with juvenile hyaline fibromatosis Get access A. Hatamochi, A. Hatamochi Department of Dermatology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321‐0293, Japan *Department of Dermatology, International University of Health and Welfare Atami Hospital, Shizuoka, Japan †Kawaguchi Dermatology Clinic, Japan E‐mail: hatamo@dokkyomed.jp.ac Search for other works by this author on: Oxford Academic Google Scholar T. Sasaki, T. Sasaki Department of Dermatology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321‐0293, Japan *Department of Dermatology, International University of Health and Welfare Atami Hospital, Shizuoka, Japan †Kawaguchi Dermatology Clinic, Japan E‐mail: hatamo@dokkyomed.jp.ac Search for other works by this author on: Oxford Academic Google Scholar T. Kawaguchi, T. Kawaguchi Department of Dermatology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321‐0293, Japan *Department of Dermatology, International University of Health and Welfare Atami Hospital, Shizuoka, Japan †Kawaguchi Dermatology Clinic, Japan E‐mail: hatamo@dokkyomed.jp.ac Search for other works by this author on: Oxford Academic Google Scholar H. Suzuki, H. Suzuki Department of Dermatology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321‐0293, Japan *Department of Dermatology, International University of Health and Welfare Atami Hospital, Shizuoka, Japan †Kawaguchi Dermatology Clinic, Japan E‐mail: hatamo@dokkyomed.jp.ac Search for other works by this author on: Oxford Academic Google Scholar S. Yamazaki S. Yamazaki Department of Dermatology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321‐0293, Japan *Department of Dermatology, International University of Health and Welfare Atami Hospital, Shizuoka, Japan †Kawaguchi Dermatology Clinic, Japan E‐mail: hatamo@dokkyomed.jp.ac Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 157, Issue 5, 1 November 2007, Pages 1037–1039, https://doi.org/10.1111/j.1365-2133.2007.08147.x Published: 01 November 2007