tbuckley/cabot-search huggingface dataset:
Lipolytic surface remnants of triglyceride-rich lipoproteins are cytotoxic to macrophages but not in the presence of high density lipoprotein. A possible mechanism of atherogenesis?
Authors: B H Chung, J P Segrest, K Smith, F M Griffin, C G Brouillette
Journal: Journal of Clinical Investigation (1989)

Hypertriglyceridemic (HTG) serum, lipolyzed in vitro by purified bovine milk lipoprotein lipase, was found to be cytotoxic to cultured macrophages. Surviving macrophages contained numerous lipid inclusions similar to those found in foam cells. Individual lipoprotein fractions isolated from the lipolyzed HTG serum, including HDL, were also cytotoxic. Lipolysis of isolated lipoprotein fractions (either HTG or normal) allowed localization of cytotoxicity to postlipolysis remnant VLDL and chylomicron particles. The presence of a critical concentration of HDL in either the lipolysis mixture or the culture dishes inhibited the cytotoxicity. Below this critical concentration HDL itself became cytotoxic, producing lipid inclusions in surviving macrophages. The lipid fraction of the cytotoxic remnants contained the cytotoxic factor(s); neither FFA nor lysolecithin alone could account for this cytotoxicity. Postprandial lipemic sera from subjects with a brisk chylomicron response, when lipolyzed in vitro, were cytotoxic to cultured macrophages; neither fasted sera from these subjects, nor postprandial sera from normolipidemic subjects with a normal chylomicron response, were cytotoxic. Postheparin (in vivo lipolyzed) serum and its isolated lipoprotein fractions obtained 30 min after heparin injection in subjects with HTG were shown to be cytotoxic to macrophages; by 60 min most of the cytotoxicity had disappeared. The postprandial and postheparin observations support an in vivo significance for remnant-associated cytotoxicity. We hypothesize that cytotoxic remnants of lipolyzed VLDL and chylomicrons may be one of the major atherogenic lipoproteins. Further, we suggest that inhibition of the cytotoxicity of these remnants may be one important way that HDL prevents atherosclerosis.
Failure to detect genetic alteration of the mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) gene in hepatocellular carcinomas in japan
Authors: Ikuo Wada, Hiroaki Kanada, Kimie Nomura, Yo Kato, Rikuo Machinami, Tomoyuki Kitagawa
Journal: Hepatology (1999)

The mannose–6–phosphate/insulin–like growth factor 2 receptor (M6P/IGF2R) suppresses cell growth through binding to the insulin–like growth factor 2 (IGF2) and latent complex of the transforming growth factor–β (TGF–β). Recently, it was reported in the United States that loss of heterozygosity (LOH) and mutations in exons 27, 28, and 31 of the M6P/IGF2R gene are frequent in hepatocellular carcinomas (HCCs) and adenomas. In view of the possible importance of this finding, especially for differential diagnosis of small hepatic lesions, we analyzed 43 primary HCCs, 2 adenomatous hyperplasias (AHs), and 3 regenerative nodules (RNs) developing in 42 Japanese patients in Japan for LOH using the polymorphic locus and for mutations by both single strand conformation polymorphism (SSCP) and direct sequencing methods. In the LOH study, 21 out of 22 informative HCCs and all of the informative AHs and RNs showed no allelic loss. In mutational studies of exons 27, 28, and 31, no mutations were detected either by SSCP or direct sequencing analysis in any of the 48 lesions. Thus inactivation of the M6P/IGF2R gene because of genetic alteration does not appear to be essential for hepatocarcinogenesis in Japan.
Prevention of infusion reactions to PEGylated liposomal doxorubicin via tachyphylaxis induction by placebo vesicles: A porcine model
Authors: János Szebeni, Péter Bedőcs, Rudolf Urbanics, Rolf Bünger, László Rosivall, Miklós Tóth, Yechezkel Barenholz
Journal: Journal of Controlled Release (2012)
Genome-wide association study identifies a susceptibility locus for HCV-induced hepatocellular carcinoma
Authors: Vinod Kumar, Naoya Kato, Yuji Urabe, Atsushi Takahashi, Ryosuke Muroyama, Naoya Hosono, Motoyuki Otsuka, Ryosuke Tateishi, Masao Omata, Hidewaki Nakagawa, Kazuhiko Koike, Naoyuki Kamatani, Michiaki Kubo, Yusuke Nakamura, Koichi Matsuda
Journal: Nature Genetics (2011)
MMPs and rheumatoid synovial fibroblasts: Siamese twins in joint destruction?
Authors: U Muller-Ladner
Journal: Annals of the Rheumatic Diseases (2002)

In this issue of the Annals, Tolboom and coworkers present functional data on the intensive invasive potential of rheumatoid synovial fibroblasts (RA-SF) into matrix as well as a direct correlation of this destructive property with distinct members of the large matrix metalloproteinase (MMP) family. 1 Key findings of this study include (a) demonstration of the higher and disease-specific ability of RA-SF-in comparison with other synovial fibroblasts-to grow through artificial matrix; (b) demonstration of a lack of correlation between invasive growth and the rate of fibroblast proliferation; (c) the dominant role of MMP-1, MMP-3, and MMP-10 in this model of a joint destructive process; and (d) the finding of an association between members of the MMP family-namely, MMP-1 and MMP-9, with the diagnosis of rheumatoid arthritis (RA).Basic as well as clinical rheumatologists may feel that the results of the study could have a direct impact on future developments in diagnosis and treatment of RA but also feel the need to discuss a number of questions arising from these interesting data.
Acupuncture for Chronic Mechanical Neck Pain
Authors: Edzard Ernst
Journal: Annals of Internal Medicine (2005)

Letters17 May 2005Acupuncture for Chronic Mechanical Neck PainEdzard Ernst, MD, PhDEdzard Ernst, MD, PhDFrom Peninsula Medical School, Universities of Exeter and Plymouth, Exeter EX2 4NTR, United Kingdom.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-142-10-200505170-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The trial by White and colleagues (1) demonstrates that, compared with placebo, acupuncture does not generate clinically relevant improvement for patients with chronic neck pain. However, this trial has at least 2 major flaws. Because there was only 1 acupuncturist, 2 dramatically different conclusions can be drawn from its findings: 1) The particular form of acupuncture used in the study was not better than placebo, or 2) the therapist was in some way inadequate. In any case, the generalizability of the result seems close to zero. In addition, there is no mention of rigorous adverse effect monitoring. ...References1. White P, Lewith G, Prescott P, Conway J. Acupuncture versus placebo for the treatment of chronic mechanical neck pain: a randomized, controlled trial. Ann Intern Med. 2004;141:911-9. [PMID: 15611488] LinkGoogle Scholar2. Dukes MNG, Aronson JK. Meyler's Side Effects of Drugs. 14th ed. Amsterdam: Elsevier; 2000. Google Scholar3. Ernst E, White A. Life-threatening adverse reactions after acupuncture? A systematic review. Pain. 1997;71:123-6. [PMID: 9211472] CrossrefMedlineGoogle Scholar4. Ioannidis JP, Evans SJ, Gøtzsche PC, O'Neill RT, Altman DG, Schulz K, et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med. 2004;141:781-8. [PMID: 15545678] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Peninsula Medical School, Universities of Exeter and Plymouth, Exeter EX2 4NTR, United Kingdom.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoBetter Reporting of Harms in Randomized Trials: An Extension of the CONSORT Statement John P.A. Ioannidis , Stephen J.W. Evans , Peter C. Gøtzsche , Robert T. O'Neill , Douglas G. Altman , Kenneth Schulz , David Moher , and Acupuncture versus Placebo for the Treatment of Chronic Mechanical Neck Pain Peter White , George Lewith , Phil Prescott , and Joy Conway Acupuncture for Chronic Mechanical Neck Pain Peter J. White and George Lewith Metrics 17 May 2005Volume 142, Issue 10Page: 873KeywordsAcupunctureAdverse eventsAnalgesicsClinical trial reportingConflicts of interest ePublished: 17 May 2005 Issue Published: 17 May 2005 CopyrightCopyright © 2005 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Weekly Epirubicin Plus Tamoxifen Versus Tamoxifen Alone As Adjuvant Treatment of Operable, Node-Positive, Elderly Breast Cancer Patients
Authors: Carol Alliot
Journal: Journal of Clinical Oncology (2005)

Armstrong was a new oncology Fellow in Manhattan (New York, NY) when the Sept. 11 World Trade Center tragedy occurred.In the November 1, 2004, issue of the Journal, she describes how the war against cancer in which she had become entrenched prevented her from mourning, grieving, and commiserating with the rest of the nation and half the world. 1 Her experiences with patients dying of cancer were too overwhelming for her to feel the loss at "Ground Zero."After learning how her own war was affecting her, she found articles in the cancer literature about programs that had been designed to aid in this process. 2,3She then sought administrative help in setting up a program to help Fellows cope with dying, pain, and suffering in their patients.By July 2003, she launched a Fellows' forum that she described as follows:Twice a month, we invited the medical oncology fellows to a lunch-time forum to discuss the psychosocial aspects of clinical oncology. 4 We encouraged fellows to share any clinical encounters that had remained with them for more than 24 hours.The sessions were cofacilitated by me and a fellow in psychiatry, with supervision from an attending physician in psychiatry.The initial sessions were gritty.Fellows appeared in great numbers and recounted stories about patients they had cared for who had stayed with them for months or even years.One fellow explained the outpouring as, "We're thirsty for this venue."The obvious need was translated into a successful program for the Fellows that has continued to this day. 5 What's striking to me is that the same need was observed during my Fellowship a third of a century ago, and a nearly identical solution was provided. 6 The sessions were held weekly exclusively for the Fellows and co-facilitated by a psychiatrist and an oncologist.Dr. Armstrong may have missed the first iteration of such a forum, perhaps because it was too long ago.In medicine, as in all endeavors of life, history does repeat itself.Most hopefully, we have learned from history to avoid a repeat of the event that occurred elsewhere in Manhattan 3 years ago.
Ferric Carboxymaltose Prevents Recurrence of Anemia in Patients With Inflammatory Bowel Disease
Authors: Rayko Evstatiev, Olga Alexeeva, Bernd Bokemeyer, Ivan Chopey, Marcel Felder, Maja Gudehus, Tariq Iqbal, Igor Khalif, Philippe Marteau, Jürgen Stein, Christoph Gasche
Journal: Clinical Gastroenterology and Hepatology (2012)
Disease and Discovery: A History of the Johns Hopkins School of Hygiene and Public Health, 1916-1939
Authors: Guenter B. Risse
Journal: JAMA (1987)

Institutional histories are often boring repositories of long-forgotten names and intramural developments, commissioned by well-meaning insiders to celebrate a particular anniversary. Refreshingly, Elizabeth Fee's book is neither tedious nor merely fashioned for in-house consumption. In fact, developments at the Hopkins School of Hygiene are merely a platform from which the author launches into a broad investigation of early 20th-century public health ideology in America. At a time when newspaper headlines and political rhetoric in the debate over the acquired immunodeficiency syndrome (AIDS) pit civil rights against public health, Fee's examination of the latter's shifting boundaries and approaches is informative. Her distinction of a medical, disease-oriented model of public health vs a social, environmental archetype is important for an understanding of the tensions and strains that still predominate in this field of study. The disease model relied heavily on the new sciences of bacteriology, medical zoology, and then virology, trying to
Geographic exposure modeling: a valuable extension of geographic information systems for use in environmental epidemiology.
Authors: J Beyea
Journal: Environmental Health Perspectives (1999)

Geographic modeling of individual exposures using air pollution modeling techniques can help in both the design of environmental epidemiologic studies and in the assignment of measures that delineate regions that receive the highest exposure in space and time. Geographic modeling can help in the interpretation of environmental sampling data associated with airborne concentration or deposition, and can act as a sophisticated interpolator for such data, allowing values to be assigned to locations between points where the data have actually been collected. Recent advances allow for quantification of the uncertainty in a geographic model and the resulting impact on estimates of association, variability, and study power. In this paper we present the terminology and methodology of geographic modeling, describe applications to date in the field of epidemiology, and evaluate the potential of this relatively new tool.
DOFETILIDE LONG-TERM EFFICACY DESPITE INABILITY TO CONVERT TO SINUS RHYTHM DURING ADMISSION FOR DRUG-INITIATION
Authors: David Lawrence, JoEllyn Abraham, Walid Saliba, Mandeep Bhargava, Michael Militello, Mark Niebauer, Stacy Poe, Carolyn Vekstein, Bruce Wilkoff
Journal: Journal of the American College of Cardiology (2014)
Sh(i)pping signals protect against Stat3-driven liver cancer
Authors: Yulia A. Nevzorova, Christian Liedtke
Journal: Hepatology (2011)

The human gene PTPN11, which encodes the tyrosine phosphatase Shp2, may act as a proto-oncogene because dominantly activating mutations have been detected in several types of leukemia. Herein we report a tumor-suppressor function of Shp2. Hepatocyte-specific deletion of Shp2 promotes inflammatory signaling through the Stat3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and development of tumors in aged mice. Furthermore, Shp2 ablation dramatically enhanced diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) development, which was abolished by concurrent deletion of Shp2 and Stat3 in hepatocytes. Decreased Shp2 expression was detected in a subfraction of human HCC specimens. Thus, in contrast to the leukemogenic effect of dominant-active mutants, Ptpn11/Shp2 has a tumor-suppressor function in liver.
Congresswoman criticises US drug plan for elderly people
Authors: Janice Tanne
Journal: BMJ (2006)

Plan D, the US Medicare drug plan that requires elderly people to sign up for a drug benefit, has been given a D for failure by a US Congressional representative in the New England Journal of Medicine (2006;354:2314-5). It “works better for the pharmaceutical and insurance industries than for beneficiaries,” she says.

Writing in a commentary, Congressional Representative Louise Slaughter of New York state, a Democrat and a microbiologist with a master's degree in public health, called Plan D “the worst abuse of the legislative process I have seen during my 20 years in Congress.”

Medicare's Plan D required all people older than 65 years to sign up for one of a confusing number of plans that offered …
Structural analysis and immunogenicity of Pseudomonas aeruginosa immunotype 2 high molecular weight polysaccharide.
Authors: G B Pier, S E Bennett
Journal: Journal of Clinical Investigation (1986)

We analyzed high molecular weight polysaccharide (PS) from the Fisher immunotype 2 (IT-2) strain of Pseudomonas aeruginosa for molecular composition and structure, then determined its immunogenicity in healthy adults. The PS was composed of 2-acetamido-2,6-dideoxygalactose (N-acetyl fucosamine) and glucose in a molar ratio of 2:1. Structural analysis by carbon-13 and proton nuclear magnetic resonance confirmed that the high molecular weight PS was structurally identical to that of the O-specific side chain of the lipopolysaccharide. PS differed from this material in molecular size. Immunization of 19 adult volunteers with doses of 50-100 micrograms of PS resulted in significant rises (P less than 0.04-P less than 0.0001) in binding antibody levels and killing antibody titers 2 and 4 wk postimmunization. The only reaction to the vaccine was localized tenderness at the immunization site. Analysis of the immunoglobulin isotype response to the vaccine showed a rise in specific serum IgG and IgA antibodies. Heterologous responses to other P. aeruginosa PS antigens were not seen. The antibody levels attained by vaccination were comparable with those in acute-phase serum samples of patients who survived sepsis with IT-2 P. aeruginosa and were significantly higher (P less than 0.03) than specific antibody levels in bacteremic patients who died. These results confirm that PS is a high molecular weight, immunogenic form of the P. aeruginosa IT-2 serotype antigen, eliciting levels of type-specific antibody comparable with those seen among patients surviving an episode of P. aeruginosa sepsis.
Primary Subclavian-Axillary Vein Thrombosis
Authors: NEIL W. SWINTON, JOSEPH W. EDGETT, ROBERT J. HALL
Journal: Circulation (1968)

Primary thrombosis of the subclavian-axillary vein is a condition of uncertain origin resulting in proximal arm swelling, discomfort on use, and prominence of engorged collateral veins in the upper arm and chest. The literature is reviewed and the authors' own experience with 23 patients, evaluated from 1950 through 1966, is detailed. This disorder is a clinically distinct venous complication of the neurovascular compression syndrome of the upper extremity. Contrary to the findings recorded by others, spontaneous improvement following conservative management, while initially good, ceases after the first few months. After a mean follow-up period of 8 years, nine patients have major, and 12 have minor, residual symptoms when using the affected arm. Venous collateral patterns persist in all patients. Early venography and thrombectomy are proposed.
Association of p53 Protein Expression With Tumor Cell Proliferation Rate and Clinical Outcome in Node-Negative Breast Cancer
Authors: D. C. Allred, G. M. Clark, R. Elledge, S. A. W. Fuqua, R. W. Brown, G. C. Chamness, C. K. Osborne, W. L. McGuire
Journal: JNCI Journal of the National Cancer Institute (1993)

Background : The p53 (also known as TP53) tumor suppressor gene encodes for a nuclear phosphoprotein thought to regulate proliferation of normal cells. Most p53 mutations result in a nonfunctional protein that accumulates in tumor cell nuclei. These common mutations appear to be involved in the development and/or progression of several neoplastic diseases including human breast cancer. Purpose : Our purpose was to investigate the relationships between levels of mutant p53 protein expression, tumor cell proliferation rate, and clinical outcome in patients with node-negative breast cancer. Methods : Expression of mutant p53 protein was evaluated by frozen-section immunohistochemistry (IHC) and light microscopy in 700 breast cancers from axillary lymph node-negative patients with long-term follow-up (median, 54 months). The immunostaining signal was expressed as the sum of scores representing the proportion and staining intensity of negative and positive tumor cell nuclei (ranges, 0 and 2–8, respectively). Statistical comparisons were made between levels of p53 protein expression and disease-free survival, overall survival, and tumor proliferation rate expressed as the percentage of cells in the S phase (%S phase) as determined by flow cytometry. Results : Of the 700 tumors, 362 (52%) showed positive nuclear immunostaining (IHC score >0). Proliferation rates were significantly higher ( P = .0001) in positive tumors (median %S phase, 7.1%) than in negative tumors (4.1%). In a univariate cutpoint analysis, negative tumors (n = 388) versus low-positive tumors (IHC score = 2–6; n = 263) versus high-positive tumors (IHC score >6; n = 99) showed progressively reduced disease-free survival (80% versus 72% versus 58% at 5 years, respectively; P ≤.05 for all pairwise comparisons). Analogous results for overall survival were 88% versus 84% versus 74%; only the result for negative versus high positive tumors was significant ( P = .003). In a multivariate analysis, expression of p53 protein and high %S phase were independently associated with reduced disease-free survival ( P = .008 and .01, respectively). Conclusions : Expression of mutant p53 protein was associated with high tumor proliferation rate, early disease recurrence, and early death in node-negative breast cancer. Despite the strong direct correlation between accumulation of p53 protein and tumor proliferation rate, both factors were independently associated with poor prognosis, suggesting that p53 may have other biological functions in addition to cell-cycle regulation. Implications : This test, when combined with other prognostic factors, may enhance our ability to identify node-negative breast cancer patients at high risk for early disease recurrence and/or death, for whom the use of adjuvant chemotherapy is unequivocally justified. [J Natl Cancer Inst 85:200–206, 1993]
Mortal Secrets: Truth and Lies in the Age of AIDS
Authors: Marla J. Gold
Journal: Annals of Internal Medicine (2004)

Medical Writings: Book Notes6 April 2004Mortal Secrets: Truth and Lies in the Age of AIDSMarla J. Gold, MDMarla J. Gold, MDFrom Drexel University School of Public Health, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-140-7-200404060-00045 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Klitzman R, Bayer R. 236 pages. Baltimore: Johns Hopkins Univ Pr; 2003. $42.00. ISBN 0801874270. Order phone 410-516-6900.Field of medicine: HIV or AIDS research, medical ethics, and psychiatry.Format: Hardcover book.Audience: Clinicians and related providers, such as case managers, who care for persons with HIV or AIDS. The concepts explored in this book should appeal to medical ethicists. In addition, issues of self-disclosure and disease should appeal to primary care physicians.Purpose: To provide a “broad yet detailed mapping of moral, social, and psychological decision making” dealing with self-disclosure of one's HIV status.Content: The book discusses self-disclosure ... Author, Article, and Disclosure InformationAffiliations: From Drexel University School of Public Health, Philadelphia, Pennsylvania. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 6 April 2004Volume 140, Issue 7Page: 588KeywordsAIDSDecision makingDisclosureHIVHIV infectionsMedical ethicsPrevention, policy, and public healthPrimary care physiciansResearch ethicsSoftware tools ePublished: 6 April 2004 Issue Published: 6 April 2004 Copyright & PermissionsCopyright © 2004 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Rationale and design of the Karolinska‐Rennes (KaRen) prospective study of dyssynchrony in heart failure with preserved ejection fraction
Authors: Erwan Donal, Lars H. Lund, Cecilia Linde, Magnus Edner, Stéphane Lafitte, Hans Persson, Fabrice Bauer, John Öhrvik, Pierre‐Vladimir Ennezat, Camilla Hage, Ida Löfman, Yves Juilliere, Damien Logeart, Geneviève Derumeaux, Pascal Gueret, Jean‐Claude Daubert
Journal: European Journal of Heart Failure (2009)