tbuckley/cabot-search huggingface dataset:
Interpretation of Genetic Test Results for Hereditary Nonpolyposis Colorectal Cancer
Authors: Sapna Syngal, Edward A. Fox, Christine Li, Marisa Dovidio, Charis Eng, Richard D. Kolodner, Judy E. Garber
Journal: JAMA (1999)

ContextGenetic testing for cancer predisposition is evolving from purely research applications to affecting clinical management.ObjectiveTo determine how often genetic test results for hereditary nonpolyposis colorectal cancer (HNPCC) can be definitively interpreted and used to guide clinical management.DesignCase-series study conducted in 1996 to 1998 in which a complete sequence analysis of hMSH2 and hMLH1 coding sequence and flanking intronic regions was performed. Mutations were categorized as protein truncating and missense. In the case of missense alterations, additional analyses were performed in an effort to assess pathogenicity.Setting and ParticipantsFamilies were identified by self-referral or health care provider referral to a cancer genetics program. Participants and kindreds were classified into 1 of 4 categories: (1) Amsterdam criteria for HNPCC, (2) modified Amsterdam criteria for HNPCC, (3) young age at onset, or (4) HNPCC-variant. In addition, each proband was classified according to the Bethesda guidelines for identification of individuals with HNPCC.Main Outcome MeasureAlterations of hMSH2 and hMLH1 genes.ResultsTwenty-seven alterations of hMSH2 and hMLH1 were found in 24 of 70 families (34.3%). Of these, deleterious mutations that could be used with confidence in clinical management were identified in 25.7% (18/70) of families. The rates of definitive results for families fulfilling Amsterdam criteria, modified Amsterdam criteria, young age at onset, HNPCC-variant, and Bethesda guidelines were 27 (39.3%), 13 (18.2%), 12 (16.7%), 11 (15.8%), and 21 (30.4%), respectively. The prevalence of missense mutations, genetic heterogeneity of the syndrome, and limited availability of validated functional assays present a challenge in the interpretation of genetic test results of HNPCC families.ConclusionsThe identification of pathogenic mutations in a significant subset of families for whom the results may have marked clinical importance makes genetic testing an important option for HNPCC and HNPCC-like kindreds. However, for the majority of individuals in whom sequence analysis of hMSH2 and hMLH1 does not give a definitive result, intensive follow-up is still warranted.
The Pathogenesis of Gluten-Sensitive Enteropathy
Authors: WARREN STROBER
Journal: Annals of Internal Medicine (1975)

Gluten-sensitive enteropathy is characterized by flattening of intestinal villi and malabsorption caused by the toxic effect of gluten, a wheat protein. Gluten activates an endogenous mechanism of toxicity that may be the local mucosal immune system: local mucosal immunoglobulin and antigluten antibody production occur soon after gluten ingestion. Approximately 80% of patients with this disease possess HL-A8, a second segregant series antigen. This association also occurs in dermatitis herpetiformis, a disease with vesicular skin lesions and gluten-sensitive flattening of intestinal villi. The association suggests that the fundamental abnormality in enteropathy is a binding reaction involving gluten protein and a binding site on a cell surface, determined in part by the histocompatibility gene; this reaction then results in a local mucosal immune response to gluten. Alternatively, the fundamental abnormality may be the presence of an abnormal immune-response gene linked to the HL-A8 gene or acting in concert with it; this immune-response gene results in local mucosal production of antigluten antibody.
Food, inglorious food
Authors: T. Delamothe
Journal: BMJ (2013)

Sex and death obsessed our immediate forebears, yet now we hardly turn a hair at their mention. Food, however, is another matter. So much about the subject is controversial.

Even one of the simplest questions—what makes us fat—is hotly contested. This week we provide space for two critics of the theory that obesity is an energy balance disorder: Gary Taubes (doi:10.1136/bmj.f1050) and Robert Lustig (doi:10.1136/bmj.f2287). Thankfully, neither wants to rewrite the laws of thermodynamics. What they do want to establish is that the insulin releasing properties of sugars such as sucrose and high fructose corn syrup are to blame for obesity. The Atkins diet—low carbohydrate, relatively high fat and protein—may have been along the right lines, after all.

Step outside …
Be wary of patients bearing gifts
Authors: D. Spence
Journal: BMJ (2010)

The NHS has a no fault, open approach to complaints; it is an organisation with “memory.” This, of course, is utter nonsense, and in reality there are witch hunts and ritualistic drownings. Obviously some complaints are justified, while others are wholly unjustified. The NHS struggles to distinguish between the two, because these are the days of health consumerism and patient power. So now doctors run scared of complaints, because they take a professional lifetime to resolve and because, irrespective of the circumstances, …
Aspiration of the Elbow Joint in the Treatment of Fractures of the Head of the Radius
Authors: T. B. Quigley
Journal: New England Journal of Medicine (1949)

IN RECENT years there has been a revival of the principle of early active motion in the treatment of elbow fractures, first expounded by Jean Pierre David1 in 1779 and vigorously restated a century later by Lucas-Championnière.2 For fractures of the radial head in particular this concept appears to be well accepted. In general, these fractures fall into three groups: those in which the fragments are so comminuted or displaced as to require arthrotomy; those in which the fragments are displaced, motion is limited, and arthrotomy is contemplated; and those in which impaction and displacement are minimal.For the first . . .
Inactivation of p53 and deletion of ATM in B-CLL patients in relation to IgVH mutation status and previous treatment
Authors: M Trbusek, J Malcikova, J Smardova, V Kuhrova, D Mentzlova, H Francova, S Bukovska, M Svitakova, P Kuglik, V Linkova, M Doubek, Y Brychtova, J Zacal, J Kujickova, S Pospisilova, D Dvorakova, J Vorlicek, J Mayer
Journal: Leukemia (2006)
Pigment Epithelium-Derived Factor Contributes to Insulin Resistance in Obesity
Authors: Seamus Crowe, Lindsay E. Wu, Catherine Economou, Sarah M. Turpin, Maria Matzaris, Kyle L. Hoehn, Andrea L. Hevener, David E. James, Elia J. Duh, Matthew J. Watt
Journal: Cell Metabolism (2009)
A SPECIFIC INACTIVATOR OF MAMMALIAN C'4 ISOLATED FROM NURSE SHARK (<i>Ginglymostoma cirratum</i>) SERUM
Authors: Joerg A. Jensen
Journal: The Journal of Experimental Medicine (1969)

A material which specifically inactivates mammalian C'4 was isolated from low ionic strength precipitates of nurse shark serum. The C'4 inactivator was not detected in whole serum. The conditions of its generation and its immunoelectrophoretic behavior seem to indicate that it is an enzymatically formed cleavage product of a precursor contained in whole shark serum. The inactivator was partially purified and characterized. It had an S-value of 3.3 (sucrose gradient) which was in agreement with its retardation on gel filtration, was stable between pH 5.0 and 10.0, had a half-life of 5 min at 56°C, pH 7.5, was inactivated by trypsin and was nontoxic. Its powerful anticomplementary activity in vitro and in vivo was solely due to the rapid inactivation of C'4; no other complement components were affected. No cofactor requirement was observed for the equally rapid inactivation of highly purified human and guinea pig C'4. The kinetics of C'4 inactivation and TAME hydrolysis, the greater anodic mobility of inactivated human C'4, and the influence of temperature on the rate of inactivation suggest that the inactivator is an enzyme and C'4 its substrate. This conclusion was supported by the more recent detection of a split product of C'4. Intravenous administration of the C'4 inactivator could prevent lethal Forssman shock and suppress the Arthus reaction in guinea pigs; it prolonged significantly the rejection time of renal xenografts but had no detectable effect on passive cutaneous anaphylaxis. Anaphylatoxin could be generated in C'4 depleted guinea pig serum with the cobra venom factor, but not with immune precipitates. The possible relationship between C'1 esterase and the C'4 inactivator is discussed on the basis of similarities and dissimilarities.
AAV vector-mediated microdystrophin expression in a relatively small percentage of mdx myofibers improved the mdx phenotype
Authors: Madoka Yoshimura, Miki Sakamoto, Madoka Ikemoto, Yasushi Mochizuki, Katsutoshi Yuasa, Yuko Miyagoe-Suzuki, Shin'ichi Takeda
Journal: Molecular Therapy (2004)

Duchenne muscular dystrophy (DMD) is a lethal disorder of skeletal muscle caused by mutations in the dystrophin gene. Adeno-associated virus (AAV) vector-mediated gene therapy is a promising approach to the disease. Although a rod-truncated microdystrophin gene has been proven to ameliorate dystrophic phenotypes, the level of microdystrophin expression required for effective gene therapy by an AAV vector has not been determined yet. Here, we constructed a recombinant AAV type 2 vector, AAV2-MCKDeltaCS1, expressing microdystrophin (DeltaCS1) under the control of a muscle-specific MCK promoter and injected it into TA muscles of 10-day-old and 5-week-old mdx mice. AAV2-MCKDeltaCS1-mediated gene transfer into 5-week-old mdx muscle resulted in extensive and long-term expression of microdystrophin and significantly improved force generation. Interestingly, 10-day-old injected muscle expressed microdystrophin in a limited number of myofibers but showed hypertrophy of microdystrophin-positive muscle fibers and considerable recovery of contractile force. Thus, we concluded that AAV2-MCKDeltaCS1 could be a powerful tool for gene therapy of DMD.
Treatment of Abdominal Aortic Aneurysms
Authors: Irwin J. Schatz
Journal: JAMA (1967)

<h3>To the Editor:—</h3> The message that I get from the report of Friedman et al (<b>200</b>:1147, 1967) is that abdominal aortic aneurysms should be excised when detected. Nevertheless, of 100 consecutive patients who had such operations in their institution, 4 died and another 24 had serious postoperative complications. The crux is to know what would have happened to these 100 patients had they not been operated upon. For this, a well-controlled, properly designed, prospective study of patients with abdominal aneurysms divided into separate categories and followed up for appropriate periods of time is necessary. Until such data are available, the argument that small abdominal aneurysms in patients with associated cardiovascular disease may be treated by careful observation (<i>Circulation</i><b>26</b>:200, 1962) is as tenable as that which suggests that all aneurysms should be removed. Unfortunately, both statements are really guesswork.
Evening primrose oil in the treatment of atopic eczema: effect on clinical status, plasma phospholipid fatty acids and circulating blood prostaglandins
Authors: MOA SCHALIN-KARRILA, LEENA MATTILA, C.T. JANSEN, PEKKA UOTILA
Journal: British Journal of Dermatology (1987)

In a double‐blind trial patients with atopic eczema received either oral evening primrose oil (EPO) (n= 14) or placebo (n= 11) for 12 weeks. In the EPO group a statistically significant improvement was observed in the overall severity and grade of inflammation and in the percentage of the body surface involved by eczema as well as in dryness and itch. Patients in the placebo group showed a significant reduction in inflammation. The patients receiving EPO showed a significantly greater reduction in inflammation than those receiving placebo. Evening primrose oil caused a significant rise in the amount of dihomogammatinolenic acid in the plasma phospholipid fatty acids. Plasma levels of TXB2, 6‐keto‐PGF1, and PGE1, and the amount of TXB2 released into serum during clotting were not altered by evening primrose oil.
Cardiotoxic Effects of Hypercatecholemia in Renal Insufficiency
Authors: W. RAAB, E. LEPESCHKIN, Y. K. STARCHESKA, W. GIGEE
Journal: Circulation (1956)

Renal insufficiency is regularly accompanied by an increase of the total catecholamines of the blood. Adrenolytic drugs, which inactivate circulating catecholamines, temporarily improve the abnormal S-T segments and T waves in patients with renal insufficiency but not in hypertensive patients without renal complications. It is suggested that in renal insufficiency, the retained circulating catecholamines damage cardiac metabolism and function. In agreement with previous observations, the behavior of the "left ventricular strain pattern" was relatively independent of the blood pressure level.
List of essential services under US health reforms is "skimpy" and dangerous, say doctors
Authors: J. Lenzer
Journal: BMJ (2011)

A national doctors’ organisation says that most of the authors of a federally sponsored report on recommended health insurance coverage have financial ties to insurers and drug companies and that the insurance scheme will leave many US citizens without access to healthcare.

The Institute of Medicine, which was contracted by the federal government to write the report, brought in security guards at the institute’s annual meeting to prevent doctors from distributing leaflets outlining the financial conflicts of interest of the report’s authors. The doctors, former institute fellows and members of Physicians for a National Healthcare Plan, were registered at the meeting and tried to give the leaflets to colleagues attending it.

Danny McCormick, assistant professor …
ACUTE KIDNEY INJURY FOLLOWING SURGERY FOR CONGENITAL HEART DISEASE: ROLE OF URINE BIOMARKERS, RENAL PERFUSION PRESSURE, AND SOMATIC OXYGEN SATURATION
Authors: David A. Hehir, John P. Scott, Kevin Regner, Matthew Buelow, Amanda J. Shillingford, Pippa Simpson, Yumei Cao, Aaron T. Dall, Briana Horn, Michael Mitchell, James Tweddell, Nancy S. Ghanayem, George Hoffman
Journal: Journal of the American College of Cardiology (2014)
Clinical Features of Bronchioloalveolar Carcinoma with New Histologic and Staging Definitions
Authors: Jon O. Ebbert, Laveena Chhatwani, Marie Christine Aubry, Jason Wampfler, Shawn Stoddard, Fang Zhang, Guibin Qiao, Mariza de Andrade, Ping Yang
Journal: Journal of Thoracic Oncology (2010)
Nonabandonment: Medical Ethics
Authors: Harvey Jay Cohen
Journal: Annals of Internal Medicine (1995)

Letters15 September 1995Nonabandonment: Medical EthicsHarvey Jay Cohen, MDHarvey Jay Cohen, MDDuke University Medical Center; Durham, NC 27710Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-123-6-199509150-00027 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read with interest the paper by Quill and Cassel [1] and the accompanying editorial [2]. Although I agree with Quill and Cassel that the concepts they propose are of extreme importance, I can see why Dr. Pellegrino would object to lumping them under the term nonabandonment. Whereas Dr. Pellegrino raises objections about the dilution of the term itself, issues relating to its appropriateness at the level of a principle, and its insufficiency and confusion as an ethical foundation, I believe that an additional objection arises from the use of a negative term when a positive one ...References1. Quill TE, Cassel CK. Nonabandonment: a central obligation for physicians. Ann Intern Med. 1995; 122:5:368-74. Google Scholar2. Pellegrino ED. Nonabandonment: an old obligation revisited [Editorial]. Ann Intern Med. 1995; 122:5:377-8. Google Scholar3. Project Professionalism. American Board of Internal Medicine; 1995:5. Google Scholar Author, Article, and Disclosure InformationAffiliations: Duke University Medical Center; Durham, NC 27710 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 September 1995Volume 123, Issue 6Page: 474KeywordsMedical ethicsPhysicians Issue Published: 15 September 1995 CopyrightCopyright © 1995 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Abstract 2410: Reduced expression of DDB2 promotes epithelial to mesenchymal transition in colon cancer
Authors: Nilotpal Roy, Pradip Raychaudhuri
Journal: Cancer Research (2012)

Abstract Invasion and metastasis are the hallmarks of malignant tumor progression and the principal cause of death related to solid tumors. Epithelial to mesenchymal transition (EMT) is intricately associated with cancer progression, as it confers cancer cells the ability to invade and metastasize to a distant organ. Here we identify a novel function of nucleotide excision repair protein DDB2 as an important antagonist of the EMT in colon carcinoma through its maintenance of epithelial phenotype. In human colon carcinoma samples, loss of DDB2 expression is highly correlated with the aggressiveness of the disease. Moreover, stimuli (TGF-beta and hypoxia) that induce EMT inhibit expression of DDB2; and loss of DDB2 is sufficient to promote EMT of colon cancer cells. The mechanism involves DDB2 mediated transcriptional repression of VEGF and MMP3. DDB2 represses these genes by histone deacetylation. We also observed that loss of DDB2 results in resistance to anoikis, an important barrier to metastasis. The lack of anoikis response is associated with increased Akt and ERK activity. Furthermore, treatment with Phenethyl Isothiocyanate (PEITC), a promising cancer chemopreventive component, augmented E-cadherin expression that is related to an increase in DDB2 expression. The present study suggests that anti-metastatic effect of PEITC involves important role of DDB2. Together, our results show that loss of DDB2 expression is both necessary and sufficient for EMT during colon carcinoma progression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2410. doi:1538-7445.AM2012-2410
Essential Role for Nitric Oxide in Neurogenic Inflammation in Rat Cutaneous Microcirculation
Authors: Radhika Kajekar, Phillip K. Moore, Susan D. Brain
Journal: Circulation Research (1995)

Abstract The possible modulatory role of nitric oxide (NO) in neurogenic edema formation in rat paw skin, induced by electrical stimulation of the saphenous nerve, was investigated by using two NO synthase inhibitors, N G -nitro- l -arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI). Both L-NAME (100 mg/kg IV, P &lt;.05) and 7-NI (10 mg/kg IV, P &lt;.05) caused an l -arginine (100 mg/kg IV, P &lt;.01)–reversible inhibition of neurogenic edema as measured by 125 I-albumin accumulation, whereas D-NAME (inactive enantiomer of L-NAME) and 6-aminoindazole (structurally similar to 7-NI) were without inhibitory effect. L-NAME produced the predicted vasopressor effect (before, 115±18 mm Hg; 5 minutes after, 174±18 mm Hg; n=6; P &lt;.05), whereas 7-NI showed no significant increase in blood pressure (before, 96±9 mm Hg; 5 minutes after, 102±10 mm Hg; n=6), and neither L-NAME nor 7-NI had any effect on basal or vasodilator calcitonin gene-related peptide (CGRP, 10 pmol per site)–stimulated local blood flow in rat skin, as measured by laser Doppler flowmetry. Furthermore, systemic and local 7-NI had no effect on edema formation induced by local administration of substance P (with or without CGRP) and histamine (with or without CGRP) in rat skin. Since 7-NI blocks edema produced by stimulation of the saphenous nerve, it is suggested that release of NO is involved in neurogenic edema formation, but the vasodilator action of NO is unimportant in this context. We suggest that NO is involved in the release of neuropeptides from sensory nerves.
Appropriateness of Spinal Manipulation
Authors: Peter G. Hill
Journal: Annals of Internal Medicine (1999)

Letters5 January 1999Appropriateness of Spinal ManipulationPeter G. Hill, DC, MPAPeter G. Hill, DC, MPASearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-130-1-199901050-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:As a chiropractor I was puzzled by Shekelle and colleagues' definition of what constitutes inappropriate use of spinal manipulation (1). The authors contradicted themselves. Let me explain.The authors state that “Few clinical indications were rated as appropriate for patients with subacute low back pain, and only 2 clinical indications were rated as appropriate for patients with chronic low back pain.”In the list of criteria for “appropriate” indications, however, the authors include “subacute low back pain, previous manipulation with favorable response” and “chronic low back pain … with favorable response.”How did the authors determine whether ...Reference1. Shekelle PG, Coulter I, Hurwitz EL, Genovese MA, Adams AH, Mior SA, et al . Congruence between decisions to initiate chiropractic spinal manipulation for low back pain and appropriateness criteria in North America. Ann Intern Med. 1998;129:9-17. LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCongruence between Decisions To Initiate Chiropractic Spinal Manipulation for Low Back Pain and Appropriateness Criteria in North America Paul G. Shekelle , Ian Coulter , Eric L. Hurwitz , Barbara Genovese , Alan H. Adams , Silvano A. Mior , and Robert H. Brook Appropriateness of Spinal Manipulation Myron M. LaBan and Ronald S. Taylor Appropriateness of Spinal Manipulation Louis Sportelli Appropriateness of Spinal Manipulation Paul G. Shekelle , Ian A. Coulter , and Robert H. Brook Metrics Cited ByLeitlinien für eine effektivere politisch-administrative Steuerung 5 January 1999Volume 130, Issue 1Page: 75KeywordsChiropracticForecastingLower back pain Issue Published: 5 January 1999 CopyrightCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Neutralizing antibodies inhibit HIV-1 transfer from primary dendritic cells to autologous CD4 T lymphocytes
Authors: Bin Su, Ke Xu, Alexandre Lederle, Maryse Peressin, Marina Elizabeth Biedma, Géraldine Laumond, Sylvie Schmidt, Thomas Decoville, Alizé Proust, Mélanie Lambotin, Vincent Holl, Christiane Moog
Journal: Blood (2012)
Positive Cancer Smears in Teenage Girls—A Warning
Authors: John M. Craig
Journal: JAMA (1962)

To the Editor:—  I wish to protest the article Positive Cancer Smears in Teenage Girls by J. H. Ferguson ( JAMA  178 :365 [Oct. 28] 1961). My first attention was drawn to this by an article in the New York Times , a tribute to its news value. I consider the article as presented, not in the best interest of medical reporting.  The article, though titled as above, deals chiefly with patients having positive  and are in fact limited to a group in whom pregnancies were almost the rule, sexual promiscuity, and infection common.  The practice of obtaining vaginal smears in young pregnant women under 20 years of age is a valuable one, but the smears must be interpreted with great caution and the diagnostic and therapeutic procedures must be approached conservatively. In this series, there would appear to be considerable looseness in grading the vaginal smears, since only 3 of