tbuckley/cabot-search huggingface dataset:
<i>SMAD2</i>,<i>SMAD3</i>and<i>SMAD4</i>Mutations in Colorectal Cancer
Authors: Nicholas I. Fleming, Robert N. Jorissen, Dmitri Mouradov, Michael Christie, Anuratha Sakthianandeswaren, Michelle Palmieri, Fiona Day, Shan Li, Cary Tsui, Lara Lipton, Jayesh Desai, Ian T. Jones, Stephen McLaughlin, Robyn L. Ward, Nicholas J. Hawkins, Andrew R. Ruszkiewicz, James Moore, Hong-Jian Zhu, John M. Mariadason, Antony W. Burgess, Dana Busam, Qi Zhao, Robert L. Strausberg, Peter Gibbs, Oliver M. Sieber
Journal: Cancer Research (2012)

Activation of the canonical TGF-β signaling pathway provides growth inhibitory signals in the normal intestinal epithelium. Colorectal cancers (CRCs) frequently harbor somatic mutations in the pathway members TGFBR2 and SMAD4, but to what extent mutations in SMAD2 or SMAD3 contribute to tumorigenesis is unclear. A cohort of 744 primary CRCs and 36 CRC cell lines were sequenced for SMAD4, SMAD2, and SMAD3 and analyzed for allelic loss by single-nucleotide polymorphism (SNP) microarray analysis. Mutation spectra were compared between the genes, the pathogenicity of mutations was assessed, and relationships with clinicopathologic features were examined. The prevalence of SMAD4, SMAD2, and SMAD3 mutations in sporadic CRCs was 8.6% (64 of 744), 3.4% (25 of 744), and 4.3% (32 of 744), respectively. A significant overrepresentation of two genetic hits was detected for SMAD4 and SMAD3, consistent with these genes acting as tumor suppressors. SMAD4 mutations were associated with mucinous histology. The mutation spectra of SMAD2 and SMAD3 were highly similar to that of SMAD4, both in mutation type and location within the encoded proteins. In silico analyses suggested the majority of the mutations were pathogenic, with most missense changes predicted to reduce protein stability or hinder SMAD complex formation. The latter altered interface residues or disrupted the phosphorylation-regulated Ser-Ser-X-Ser motifs within SMAD2 and SMAD3. Functional analyses of selected mutations showed reductions in SMAD3 transcriptional activity and SMAD2-SMAD4 complex formation. Joint biallelic hits in SMAD2 and SMAD3 were overrepresented and mutually exclusive to SMAD4 mutation, underlining the critical roles of these three proteins within the TGF-β signaling pathway.
Drinking Coffee and Carbonated Beverages Blocks Absorption of Nicotine From Nicotine Polacrilex Gum
Authors: Jack E. Henningfield, Aleksandras Radzius, Thomas M. Cooper, Richard R. Clayton
Journal: JAMA (1990)

Patients failing to obtain benefit from nicotine polacrilex gum in their efforts to quit smoking may be inadvertently blocking nicotine absorption. Effective nicotine absorption depends on the mildly alkaline saliva that is produced when buffering agents in the polacrilex are released along with nicotine as the polacrilex is chewed. We found that intermittent mouth rinsing with coffee or cola, but not distilled water, substantially reduced salivary pH and nicotine absorption. Because many commonly consumed substances were also found to be highly acidic, we recommend that patients do not ingest any substance during or immediately before nicotine polacrilex use. (<i>JAMA</i>. 1990;264:1560-1564)
PURE CULTIVATION OF SPIROCHÆTA PHAGEDENIS (NEW SPECIES), A SPIRAL ORGANISM FOUND IN PHAGEDENIC LESIONS ON HUMAN EXTERNAL GENITALIA
Authors: Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1912)

1. A hitherto undescribed spiral organism has been isolated in pure culture from a case of mild phagedenic ulcer on the external genitalia of a woman. For this organism the name Spirochœta phagedenis is proposed. 2. Spirochœta phagedenis is a strict anaerobe and grows in the presence of fresh tissue in ascitic agar. It produces no apparent change in the media, but a somewhat offensive odor develops in the culture tube. 3. Spirochœta phagedenis incites a slight inflammatory reaction in the skin of a Macacus rhesus monkey and in the skin and testicles of rabbits. 4. Its etiological relation to the phagedenic lesions on the external genitalia has not yet been determined.
Biallelic mutation of SOCS-1 impairs JAK2 degradation and sustains phospho-JAK2 action in the MedB-1 mediastinal lymphoma line
Authors: Ingo Melzner, Alexandra Juliana Bucur, Silke Brüderlein, Karola Dorsch, Cornelia Hasel, Thomas F. E. Barth, Frank Leithäuser, Peter Möller
Journal: Blood (2004)
THE DIFFERENTIAL DIAGNOSIS OF CHOLELITHIASIS.
Authors: GEORGE W. WEBSTER
Journal: JAMA (1895)

Two quarts of ice water are generally used to which in some cases tannic acid may added; also lysol, one ounce to one quart of water ; liquid soap; inspissated ox-gall to one quart of water.Constipation is also much improved by eating bran gems three times a day with meals.Common bran from the feed store is used in making these.ADVANTAGES OF BRAN GEMS.
Prevalence of asthma, rhinoconjunctivitis and atopic eczema among Brazilian adolescents. Comparison between ISAAC phases I and III*1
Authors: D. Solé, I.C.C. Nunes, N.A. Rosário, L.S. Freitas, M. Brito, K. Melo, R. Stein, G.B. Fisher, C.K. Naspitz
Journal: Journal of Allergy and Clinical Immunology (2004)
AXIAL TORSION OF A FULL-TERM PREGNANT UTERUS
Authors: Ralph A. Reis
Journal: JAMA (1935)

The pregnant uterus usually shows some degree of torsion during the latter half of pregnancy. Such torsion is merely an exaggeration of the physiologic rotation of the pregnant uterus. This usual type of rotation is readily seen at laparotomy, especially at term. It consists of a longitudinal twist of a few degrees. The twist is to the right in 80 per cent of patients and to the left in only 20 per cent. Torsion of this type has no major clinical significance. True axial rotation of the pregnant uterus is rare and serious. Sudden rotation of the uterus on its long axis through more than 90 degrees may result in premature separation of the placenta, hemorrhage, profound shock and the symptoms of acute peritonitis. When it occurs, it is usually in association with uterine tumors or malformations. Robinson and Duvall<sup>1</sup>have stated that "without uterine abnormalities there can be no
A NATIONWIDE SURVEY OF ADOPTION AND PERCEPTION OF PHARMACOGENOMIC TESTING BY U.S. CARDIOLOGISTS
Authors: Eric Stanek, Christopher L. Sanders, Barnabie C. Agatep, Katherine A. Johansen, Ronald E. Aubert, Mona Khalid, Aanal Patel, Felix W. Frueh, Robert S. Epstein
Journal: Journal of the American College of Cardiology (2011)
Public Health Effects of Occupational and Environmental Radiation Exposure
Authors: Russell A. Brown
Journal: JAMA (1991)

To the Editor.  —Wing et al1reported a 63% elevation of leukemia mortality (28 deaths observed, 17.2 deaths expected) in a population of Oak Ridge (Tenn) National Laboratory white male employees with a median cumulative radiation dose of 1.4 mSv or 0.14 rem; the 95% confidence interval for the standardized mortality ratio (SMR) was 1.08 to 2.35. Although the total cancer SMR was 21% lower than normal, a radiation-cancer dose response of 4.94% per 10 mSv (1 rem) was claimed for all cancers.  The analysis  invalid. Seven of the 28 leukemia deaths were caused by chronic lymphocytic leukemia (CLL), which has been clearly identified as nonradiogenic by all major studies of cancer and radiation.2-5Wing et al noted that CLL is not in some lists of radiation-related leukemia, but used the CLL data to calculate the SMR and predict dose-response factors for radiogenic leukemia.  The effect of
Vasodepressor Syncope
Authors: A. M. WEISSLER, J. V. WARREN, E. H. ESTES, H. D. MCINTOSH, J. J. LEONARD
Journal: Circulation (1957)

Vasodepressor syncope is characterized hemodynamically by a sudden fall in total peripheral resistance with little associated change in cardiac output. The failure of the cardiac output to compensate for the fall in peripheral resistance is a striking feature of the fainting reaction. Possible explanations for this phenomenon are the presence of neurogenic myocardial inhibition or markedly limited volume of blood available to the heart. The effects of atropine injections, inflation of antigravity suit, negative pressure breathing, and albumin infusions on the syncopal reaction were studied. Results favor the causative role of limited venous inflow in the cardiac output response.
Drug and water firms attack EU plan to reduce ethinylestradiol pollution
Authors: R. McKie
Journal: BMJ (2012)

The drug industry is heading for confrontation with green campaigners over a European Parliament proposal to clean up rivers, streams, and drinking water supplies contaminated by synthetic hormones from contraceptive pills.

Ecologists say the chemical poses a serious threat to wildlife. Water and drug companies argue that the high cost of the plan is not justified by the risk. One estimate suggests a hormone clean up would raise water purification costs in the UK by £30bn (€37bn; $46bn) over 10 years.

Ethinylestradiol (EE2), the main active ingredient of contraceptive pills, is excreted and washed into sewage systems and rivers and has been found at sites throughout Europe. Even at very low concentrations, it has been shown …
Acromegaly and Hyperparathyroidism
Authors: P. J. B. Hubner
Journal: BMJ (1967)

BMEDICALORNALtion by practising on stillborn infants.As a precaution a Cardiff connector could be fitted to the tube before insertion (Fig. 2).Possible modifications of the tube itself include increasing the overall length, fitting a collar or crosspiece, or simply attaching a plastic tail to enable easy withdrawal.If the ease with which a tube can be lost is appreciated this accident is unlikely to occur.
Reply to Robert P. Myers’ Letter to the Editor re: Francesco Montorsi, Timothy G. Wilson, Raymond C. Rosen, et al. Best Practices in Robot-assisted Radical Prostatectomy: Recommendations of the Pasadena Consensus Panel. Eur Urol 2012;62:368–81
Authors: Vincenzo Ficarra, Giacomo Novara, Alexandre Mottrie, Timothy G. Wilson, Francesco Montorsi
Journal: European Urology (2012)
NAD Biosynthesis Evolution in Bacteria: Lateral Gene Transfer of Kynurenine Pathway in Xanthomonadales and Flavobacteriales
Authors: W. C. Lima, A. M. Varani, C. F.M. Menck
Journal: Molecular Biology and Evolution (2008)

The biosynthesis of quinolinate, the de novo precursor of nicotinamide adenine dinucleotide (NAD), may be performed by two distinct pathways, namely, the bacterial aspartate (aspartate-to-quinolinate) and the eukaryotic kynurenine (tryptophan-to-quinolinate). Even though the separation into eukaryotic and bacterial routes is long established, recent genomic surveys have challenged this view, because certain bacterial species also carry the genes for the kynurenine pathway. In this work, both quinolinate biosynthetic pathways were investigated in the Bacteria clade and with special attention to Xanthomonadales and Bacteroidetes, from an evolutionary viewpoint. Genomic screening has revealed that a small number of bacterial species possess some of the genes for the kynurenine pathway, which is complete in the genus Xanthomonas and in the order Flavobacteriales, where the aspartate pathway is absent. The opposite pattern (presence of the aspartate pathway and absence of the kynurenine pathway) in close relatives (Xylella ssp. and the order Bacteroidales, respectively) points to the idea of a recent acquisition of the kynurenine pathway through lateral gene transfer in these bacterial groups. In fact, sequence similarity comparison and phylogenetic reconstruction both suggest that at least part of the genes of the kynurenine pathway in Xanthomonas and Flavobacteriales is shared by eukaryotes. These results reinforce the idea of the role that lateral gene transfer plays in the configuration of bacterial genomes, thereby providing alternative metabolic pathways, even with the replacement of primary and essential cell functions, as exemplified by NAD biosynthesis.
Reduced‐intensity bone marrow transplantation from an alternative unrelated donor for myelodysplastic syndrome of first‐donor origin
Authors: Yukiko Komeno, Yoshinobu Kanda, Koji Kandabashi, Masahito Kawazu, Susumu Goyama, Masataka Takeshita, Yasuhito Nannya, Miyuki Niino, Tetsuya Nakamoto, Mineo Kurokawa, Shiho Tsujino, Seishi Ogawa, Katsunori Aoki, Shigeru Chiba, Toru Motokura, Hisamaru Hirai
Journal: American Journal of Hematology (2003)

Abstract A male patient had a relapse of myelodysplastic syndrome (MDS) 2 years after BMT from a female matched unrelated donor. Conventional cytogenetics, FISH, and short‐tandem repeat chimerism analysis proved a relapse of donor origin. He underwent reduced‐intensity BMT after a conditioning with fludarabine and busulfan, since he had impaired renal, liver, and pulmonary functions. Chimerism analysis on day 28 after the second BMT showed mixed chimerism of the first and the second donors, which later turned to full second‐donor chimerism on day 60. He developed grade II acute GVHD of the skin and cytomegalovirus reactivation, but both were improved with methylprednisolone and ganciclovir, respectively. He remains in complete remission 6 months after the second BMT. Reduced‐intensity second BMT from an alternative donor appeared to be a tolerable treatment option for donor‐derived leukemia/MDS after the first conventional transplantation. Am. J. Hematol. 72:220–222, 2003. © 2003 Wiley‐Liss, Inc.
EndoResect study: endoscopic full-thickness resection of gastric subepithelial tumors
Authors: C. Schlag, D. Wilhelm, S. von Delius, H. Feussner, A. Meining
Journal: Endoscopy (2012)

<b>Background and study aims: </b>Endoscopic resection of gastric subepithelial tumors (SETs) carries a high risk of perforation. New techniques such as use of the over-the-scope clip (OTSC) may enable secure endoscopic closure of perforations. We aimed to evaluate the feasibility of endoscopic resection of small gastric SETs using a grasp-and-snare technique followed by OTSC closure of the gastric wall if necessary. <b>Patients and methods:</b> In this prospective study 20 consecutive patients who presented with gastric SETs ≤ 3 cm were enrolled. Endoscopic resection was performed using a double-channel endoscope, a tissue anchor and a monofilament snare. If perforation occurred, the aim was to achieve complete closure with a tissue twin grasper and the OTSC. Procedures were performed under laparoscopic control using a 5-mm optic, which was introduced via a single 5-mm trocar through the umbilicus. All patients were followed up for 3 months after the procedure. <b>Results:</b> In 6 /20 patients a pure endoscopic approach was impossible and a switch to laparoscopic wedge resection was necessary (large tumor size in 2 /6 patients; mainly extraluminal growth in 4 /6 patients). Solely endoscopic resection was successfully performed in the remaining 14 patients. Amongst these, laparoscopic control was impossible in two cases. Perforation occurred in 6 /14 patients but gastric closure with the OTSC was performed successfully in all these cases. No complications occurred and follow-up was unremarkable. <b>Conclusion:</b> Endoscopic snare resection enables safe treatment of small gastric SETs (diameter ≤ 3 cm) and seems faster and easier to perform than other endoscopic resection techniques, such as endoscopic submucosal dissection (ESD) or submucosal tunneling. Perforations occurring after full-thickness resection can be adequately managed by OTSC closure. Solely endoscopic resection without laparoscopic control seems possible in selected patients with tumors known to have purely intraluminal growth.
DIAGNOSING EPIDERMOLYSIS BULLOSA
Authors: R.A.J. Eady, M.J. Tidman
Journal: British Journal of Dermatology (1983)

Journal Article DIAGNOSING EPIDERMOLYSIS BULLOSA Get access R.A.J. Eady, R.A.J. Eady Department of Electron Microscopy and Cell Pathology, Institute of Dermatology, Homerton Grove, London E9 6BX Dr R.A.J. Eady Search for other works by this author on: Oxford Academic Google Scholar M.J. Tidman M.J. Tidman Department of Electron Microscopy and Cell Pathology, Institute of Dermatology, Homerton Grove, London E9 6BX Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 108, Issue 5, 1 May 1983, Pages 621–626, https://doi.org/10.1111/j.1365-2133.1983.tb01067.x Published: 01 May 1983
Medical Costs-Reply
Authors: Stephen J. Dresnick
Journal: JAMA (1980)

<h3>In Reply.—</h3> We have the impression that Dr Finley has placed the cart before the horse. He points out that the inherent costs of running a hospital are great and that hospitals are having financial difficulties. He suggests that physicians should maximize efficiency by altering their ordering habits so as to meet "thresholds." The fact remains that the practice of medicine is the total knowledge that the physician has acquired through schooling and experience, together with the judicious choice of diagnostic procedures and therapeutics. It is the obligation of every physician to order only what is necessary. Increased awareness of the cost of medical care may provide an added stimulus for physicians to review more critically their reasons for ordering supplies, laboratory tests, and services for their patients. If, as a result of the prudent practice of medicine by physicians, there are losses of income in selective departments in a
Allowing or Causing Death
Authors: JOSEPH E. SCHERGER
Journal: Annals of Internal Medicine (1978)

Letters and Corrections1 February 1978Allowing or Causing DeathJOSEPH E. SCHERGER, M.D.JOSEPH E. SCHERGER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-88-2-270_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I found the article by K. Danner Clouser, "Allowing or Causing: Another Look" (Ann Intern Med 87:622-624, 1977), quite interesting. I agree with his position that the difference between "allowing to die" and "causing to die" is subtle. However, I object to his notion that "it is the doctor's obligation to do all he can to save," and that if the physician recedes from this, he ethically becomes a layman.It has become axiomatic in medicine that the physician will cure sometimes, but comfort always. As eloquently described by Peabody (1), the caring role of a physician...Reference1. PEABODY F: The care of the patient. JAMA 88:877-882, 1927 CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 February 1978Volume 88, Issue 2Page: 270-271 Issue Published: 1 February 1978 PDF DownloadLoading ...
The Death of a Baby: Neither Forgiven Nor Forgotten-Reply
Authors: Gerald B. Hickson
Journal: JAMA (1992)

<h3>In Reply.</h3> —This story unfortunately is typical of many cases we examined in seeking to identify factors prompting families to file malpractice claims. In almost all cases, and independent of determinations of liability, families indicated that there were problems with patient-physician communication and that these problems were often "the last straw" in their decisions to file claims. Many told us they pursued litigation even though they realized that the process might rekindle old feelings of grief and subject them to the trauma of the courtroom. This case illustrates several of our findings. Mr Feilich said: "Afterward, we tried to call the group," and "No one returned our calls." Few patients in our study believed that their physicians returned such calls in a timely manner. While we can only speculate about the reasons for this seeming reluctance, at least some hesitancy may relate to physicians' lack of training in how to
Women in Clinical Trials — A Portfolio for Success
Authors: Julie E. Buring
Journal: New England Journal of Medicine (2000)

Just a decade ago, in September 1990, public and political concern about the underrepresentation of women in major clinical trials,1 especially trials focusing on cardiovascular disease, resulted in the establishment of the Office of Research on Women's Health by the National Institutes of Health (NIH). The mission of the office was to set an agenda for research on women's health and to ensure that women and members of minority groups would be included in clinical research funded by the NIH. Three years later, the NIH Revitalization Act required that the NIH strengthen its policies to ensure not only that women . . .
Fatal Massive Hepatic Necrosis Following Acetaminophen Overdose
Authors: Brittain McJunkin
Journal: JAMA (1976)

A young woman ingested approximately 13 gm of an over-the-counter acetaminophen preparation and died seven days later in profound coma. Postmortem findings included massive centrilobular hepatic necrosis and renal tubular necrosis. Although hepatotoxicity secondary to acetaminophen overdose is well recognized in Britain, this entity has received little emphasis in the United States. Recognition of the potentially severe consequences is important because early treatment with sulfhydryl compounds may prevent serious liver injury.
USEFULNESS OF ELECTROCARDIOGRAPHIC PARAMETERS AS COMPARED TO COMPUTED TOMOGRAPHY MEASURES OF LEFT ATRIAL VOLUME ENLARGEMENT: FROM THE ROMICAT TRIAL
Authors: Quynh A. Truong, Elizabeth M. Charipar, Leon Ptaszek, Carolyn Taylor, Joao D. Fontes, Matthias Kriegel, Thomas Irlbeck, Amir A. Mahabadi, Fabian Bamberg, Ron Blankstein, Thomas J. Brady, John T. Nagurney, Udo Hoffmann
Journal: Journal of the American College of Cardiology (2010)
Reversible Regulation of the Transformed Phenotype of Ornithine Decarboxylase- and Ras-Overexpressing Cells by Dominant-Negative Mutants of c-Jun
Authors: Mari Kielosto, Pirjo Nummela, Riikka Katainen, Virna Leaner, Michael J. Birrer, Erkki Hölttä
Journal: Cancer Research (2004)

Abstract c-Jun is an oncogenic transcription factor involved in the regulation of cell proliferation, apoptosis and transformation. We have previously reported that cell transformations induced by ornithine decarboxylase (ODC) and c-Ha-ras oncogene, commonly activated in various cancer cells, are associated with constitutively increased phosphorylation of c-Jun on Ser residues 63 and 73. In the present study, we examined the significance of c-Jun phosphorylation and activation on the phenotype of the ODC- and ras-transformants, by using specific inhibitors and dominant-negative (DN) mutants to c-Jun NH2-terminal kinase (JNK) and its upstream kinase, SEK1/MKK4 (mitogen-activated protein kinase kinase 4), and to c-Jun. The transformed morphology of both the ODC- and ras-expressing cells was reversed partially by JNK inhibitors and DN JNK1, more effectively by DN SEK1/MKK4 and phosphorylation-deficient c-Jun mutants (c-JunS63,73A, c-JunS63,73A,T91,93A) and most potently by a transactivation domain deletion mutant of c-Jun (TAM67). Moreover, tetracycline-inducible TAM67 expression in ODC- and ras-transformed cells showed that the transformed phenotype of the cells is reversibly regulatable. TAM67 also inhibited the tumorigenicity of the cells in nude mice. These inducible cell lines, together with their parental cell lines, provide good models to identify the genes and proteins relevant to cellular transformation.
HYDROXYUREA: A NEW ANTIMETABOLITE IN THE TREATMENT OF PSORIASIS
Authors: MORRIS ROSTEN
Journal: British Journal of Dermatology (1971)

SUMMARY.— A short term study of the treatment of 12 cases of refractory psoriasis with hydroxyurea is reported. Before commencing treatment, each patient's Hb., W.B.C. and platelets were determined and liver and renal function tests were performed. The dose of hydroxyurea varied from 1.5 to 2.0 g daily and treatment was continued until a maximal therapeutic response was obtained. All cases were evaluated at weekly intervals and weekly determinations of W.B.C, Hb. and platelets were made. Six of the patients were favourably affected, 2 showed no change after 8 weeks of treatment and 4 discontinued treatment because of side effects.