tbuckley/cabot-search huggingface dataset:
Novartis challenges India's drug patent laws in Supreme Court
Authors: M. Billingsley
Journal: BMJ (2012)

The interpretation of India’s drug patent laws is being challenged in the country’s Supreme Court by the drug company Novartis. Campaigners say that if the challenge is successful it will restrict access of developing countries to generic drugs.

Novartis is seeking a new patent for the anticancer drug imatinib mesilate (which it markets as Glivec) in a case that will begin in the court on 28 February.

But the charity Medecins Sans Frontieres (MSF) argues that the case should be rejected because it concerns a tweak to an existing formulation of the drug—a technique known as “evergreening”—and does not represent an improvement in clinical effectiveness, as required under section 3(d) of India’s patent laws.

MSF fears that if Novartis is successful the Indian Patents Office will be under pressure to award more patents for drugs with minor modifications, which could see …
Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2
Authors: Henryk Dreger, Kera Westphal, Nicola Wilck, Gert Baumann, Verena Stangl, Karl Stangl, Silke Meiners
Journal: Cardiovascular Research (2009)

Increased levels of reactive oxygen species cause oxidative stress and severely damage lipids, proteins, and DNA. We have previously shown that partial proteasome inhibition induces an antioxidative gene pattern in endothelial cells. Here, we elucidate the mechanisms of proteasome inhibitor-mediated upregulation of antioxidative enzymes and cytoprotection. Non-toxic proteasome inhibition upregulated mRNA and protein expression of superoxide dismutase 1 (SOD1) and haem oxygenase 1 (HO1) in several human endothelial and vascular smooth muscle cell types. Transcriptional activation of these enzymes was shown by inhibition of RNA polymerase II and nuclear run-on assays. Transfection of endothelial cells with luciferase reporter constructs revealed that upregulation can be largely confined to an antioxidant response element (ARE), which proved to be sufficient for transcriptional activation of SOD1 and HO1. Co-transfection studies and bandshift analyses confirmed binding of the antioxidative transcription factor NF-E2-related factor 2 (Nrf2)—which was stabilized by proteasome inhibition as shown by immunoblots—to the ARE site of HO1. Experiments with aortic endothelial and smooth muscle cells from Nrf2 wild-type and knockout mice revealed an essential role of Nrf2: in wild-type cells, proteasome inhibitor-mediated induction of SOD1 and HO1 was accompanied by protection of vascular cells against oxidative stress as determined by lactate dehydrogenase release assays. In contrast, proteasome inhibitor-mediated induction of antioxidative enzymes and cytoprotection were completely lost in cells from Nrf2 knockout mice. Nrf2-dependent transcriptional activation of antioxidative enzymes is crucial for proteasome inhibitor-mediated protection of vascular cells against oxidative stress.
The Effect of Human Tumor Extracts Upon Autologous Peripheral Blood Lymphocytes.
Authors: Herbert Savel
Journal: Annals of Internal Medicine (1969)

s1 May 1969The Effect of Human Tumor Extracts Upon Autologous Peripheral Blood Lymphocytes.Herbert Savel, M.D.Herbert Savel, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1106_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe induction of lymphocyte transformation by various antigens has been shown to be a direct reflection of the degree of lymphocytic or delayedtype immunity in the host. Since specific lymphocyte immunity has been shown to effect regression of transplanted animal tumors, the degree of tumordirected lymphocyte immunity was studied in human cancer. The degree of lymphocyte transformation induced by saline extracts of autologous tumors was determined in 44 patients with cancer. Cultures of peripheral blood lymphocytes were incubated in duplicate with cell-free extracts of autologous tumors (in concentration of 1 to 300 mg protein/ml) and the degree of stimulation determined... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Herbert Savel, M.D.Affiliations: Burlington, Vermont PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1106-1106KeywordsAntigensAttentionBloodImmunityLymphocytesProteins ePublished: 1 December 2008 Issue Published: 1 May 1969 PDF downloadLoading ...
Busulfan (Myleran) for Myelocytic Leukemia
Authors: John W. Frost
Journal: JAMA (1965)

<h3>To the Editor:—</h3> In your issue of July 19 (<b>193</b>:255, 1965), there is a question in regard to the treatment of chronic myelocytic leukemia. This is answered by Dr. John W. Frost with the unequivocal statement that "Busulfan (Myleran) is the treatment of choice in chronic myelocytic leukemia." Although this may be true, I have seen no report of the results of treatment with Busulfan, which are comparable to the number of cases treated, or the results of treatment, reported as the result of treatment by means of x-ray or radioactive phosphorus. J. H. Lawrence reported on the latter in 1954; Osgood and associates reported on a comparison of x-ray treatment with that of irradiated phosphorus in 1955; also, a report of my treatment has appeared in a relatively small series, published both in Germany and America, in 1961. Until it has been demonstrated by adequate comparisons, it seems
Accelerated Leukemogenesis by Truncated CBFβ-SMMHC Defective in High-Affinity Binding with RUNX1
Authors: Yasuhiko Kamikubo, Ling Zhao, Mark Wunderlich, Takeshi Corpora, R. Katherine Hyde, Thomas A. Paul, Mondira Kundu, Lisa Garrett, Sheila Compton, Gang Huang, Linda Wolff, Yoshiaki Ito, John Bushweller, James C. Mulloy, P. Paul Liu
Journal: Cancer Cell (2010)
Preoperative Screening for Sickle Cell Trait
Authors: Santosh Kalhan
Journal: JAMA (1988)

<h3>To the Editor.</h3> —Dr Eichhorn<sup>1</sup>gives several reasons against the routine preoperative screening of black patients for sickle cell trait. However, based on available published data, the issue is far from being resolved. All patients with hemoglobin SS disease will not necessarily have been clearly diagnosed prior to the administration of anesthesia. Powars<sup>2</sup>describes seven children under 5 years of age not suspected of having any illness who were demonstrated to have hemoglobin SS disease on postmortem studies following sudden death. Death was also the presenting manifestation of undiagnosed hemoglobin SS disease in three children in the Cincinnati area.<sup>3</sup>There are several references in the medical literature on increased morbidity and mortality in sickle cell trait with anesthesia, and even if these are anecdotal they cannot be completely ignored.<sup>4,5</sup> While it is true that all patients must have adequate oxygenation during all types of anesthesia, prior
Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in american patients
Authors: Jorge A. Marrero, Grace L. Su, Wei Wei, Dawn Emick, Hari S. Conjeevaram, Robert J. Fontana, Anna S. Lok
Journal: Hepatology (2003)

Mortality due to hepatocellular carcinoma (HCC) has not improved over the last 20 years. This is in part due to the poor performance of available tumor markers leading to delays in diagnosis. Des–gamma carboxy–prothrombin (DCP) has been reported to be more sensitive and specific for the diagnosis of HCC in Japanese patients compared with α–fetoprotein (AFP). We conducted a cross–sectional case control study to evaluate whether DCP is more sensitive and specific than AFP for differentiating HCC from nonmalignant liver disease in a cohort of American patients from a single referral center. Four groups were studied: G1, normal healthy subjects; G2, patients with noncirrhotic chronic hepatitis; G3, patients with compensated cirrhosis; and G4, patients with histologically proven HCC. A total of 207 subjects were enrolled. Both DCP and AFP levels increased progressively from G1 to G4, but DCP values had less overlap among the groups than AFP. ROC curve indicated that a DCP value of 125 mAU/mL yielded the best sensitivity (89%; 95% CI, 77%–95%) and specificity (95%; 95% CI, 82%–96%) for differentiating patients with HCC from those with cirrhosis and chronic hepatitis. The optimal AFP cutoff value was 11 ng/mL and was inferior to the DCP value of 125 mAU/mL, the area under the ROC curves being 0.928 versus 0.810, respectively ( P = .002). In conclusion, DCP was more sensitive and specific than AFP for differentiating HCC from nonmalignant chronic liver disease. Prospective studies to evaluate the role of DCP in early HCC are underway.
Underrepresentation of Women in New Drug Trials
Authors: Evlin L. Kinney, Joanne Trautmann, Jay Alexander Gold, Elliot S. Vesell, Robert Zelis
Journal: Annals of Internal Medicine (1981)

Young women serve less frequently than young men as subjects in premarketing clinical drug trials. Moral, legal, and medical implications of this underrepresentation of women are considered. Risks of medical harm to female patients can increase because medication is withheld. Also, risks of toxicity increase when women receive certain new drugs only in the postmarketing phase. Remedies to increase participation of young, nonpregnant women in clinical trials are discussed.
THE MATHEMATICS OF THE DIABETIC DIET.
Authors: ALFRED C. CROFTAN
Journal: JAMA (1904)

There is a popular prejudice to the effect that glycosuria calls for complete withdrawal of carbohydrates. This is occasionally good practice. In the majority of cases, however, it is superfluous, and imposes unnecessary hardship on the sufferer; and in many cases it is decidedly bad practice and dangerous. This routine treatment is to be condemned on two grounds chiefly, viz., (1) because it is almost impossible to adequately nourish these patients unless the carbohydrate is replaced, bulk for bulk, by other food equivalents; (2) because the complete withdrawal of the carbohydrates eminently favors the development of acidosis, and incidentally precipitates the almost inevitable consequence of acidosis, viz., diabetic coma. I venture to say that failure to mathematically regulate the nutrition of sufferers from diabetes, in innumerable cases leads to death from slow starvation, and that complete and injudicious withdrawal of the carbohydrate elements of the food precipitates the development of
Bleeding Duodenal Ulcer Control
Authors: Robert I. White
Journal: JAMA (1974)

Previous attempts to control bleeding duodenal ulcers by intra-arterial infusion of vasoconstrictors have been largely ineffective. We have employed embolization of autologous blood clot to successfully control hemorrhage in a duodenal ulcer patient who was a poor surgical risk and whose hemorrhage was unresponsive to vasopressin administered intra-arterially. At present it is suggested that this form of therapy be utilized in patients with large-vessel bleeding, who are poor surgical risks and whose bleeding is unresponsive to intra-arterially given vasoconstrictors. (<i>JAMA</i>229:546-548, 1974)
Containing the AIDS Epidemic
Authors: Neil Schram
Journal: JAMA (1985)

To the Editor.—  The editorial by Dr Lundberg 1 discusses some preventive measures for people to take to protect themselves from the acquired immunodeficiency syndrome (AIDS) virus. Although those practices were described as simple in the editorial, the implementation of the last three is virtually impossible at present even for someone who is willing to comply.  Persons who are carrying the AIDS virus should not become pregnant. To implement that advice, any female who is considering pregnancy should be tested for the AIDS virus. How? The only tests readily available at present are antibody tests. While a positive confirmed test result is probably significant, a negative result does not ensure freedom from infection: first, the result of an antibody test does not become positive until sometime after infection. Second, as reported in the same issue of JAMA by Carlson et al, 2 ten of 69 AIDS patients were negative in
Abstract 2954: TWIST1 is a critical mediator of KRAS mutant tumorigenesis in human non-small cell lung cancer
Authors: Timothy F. Burns, Irina Dobromilskaya, Sara C. Murphy, Rajendra P. Gajula, Khaled Aziz, Yoon-Jae Cho, Phuoc T. Tran, Charles M. Rudin
Journal: Cancer Research (2012)

Abstract A large fraction of non-small cell lung cancers (NSCLC) have mutant KRAS, which is associated with poor response to current cytotoxic therapy and a poor prognosis. Although the KRAS signaling pathway has been well characterized, no current therapies target this critical oncogene. Several studies have demonstrated that bypass of senescence in Kras-mediated adenocarcinoma mouse models is essential for tumorigenesis. Therefore, activation of senescence in KRAS mutant NSCLC may be an effective therapeutic strategy. We recently demonstrated that the basic helix loop helix transcription factor Twist1 cooperates with mutant Kras to induce lung adenocarcinoma in transgenic mouse models and that inhibition of Twist1 in these models led to activation of Kras-induced senescence and tumor stasis. In the current study, we examine the role of TWIST1 in KRAS mutant human NSCLC. Silencing of TWIST1 in multiple KRAS mutant NSCLC cell lines resulted in dramatic growth inhibition and either reactivation of oncogene-induced senescence or in some cases, apoptosis. Similar effects were also observed in four KRAS wild type lines, including cell lines with key driver mutations including a cell line with an activating EGFR mutation and a cell line with c-Met amplification. Gene set enrichment analysis of NSCLC cell lines after silencing of TWIST1 revealed a striking cell cycle arrest gene signature. Growth inhibition by silencing of TWIST1 was independent of p53 or Rb/p16 mutational status. Furthermore, activation of oncogene-induced senescence by TWIST1 silencing did not require previously defined mediators of senescence, p21 and p27, nor could this phenotype be rescued by overexpression of SKP2. To extend these observations in vivo, TWIST1 was silenced in both KRAS mutant and wildtype cell lines and these cells were implanted in NOD-SCID mice to assess tumor formation. Interestingly, silencing of TWIST1 in xenograft models preferentially inhibited KRAS mutant tumor formation suggesting that TWIST1 plays a critical in mediating KRAS tumorigenesis. Finally, inducible silencing of TWIST1 resulted in significant growth inhibition of established xenograft KRAS mutant tumors. Together these findings suggest TWIST1 is essential for the establishment and maintenance of KRAS mutant NSCLC tumors and silencing of TWIST1 in KRAS mutant NSCLC represents a novel and promising therapeutic strategy. 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 2954. doi:1538-7445.AM2012-2954
THE BOY'S VENEREAL PERIL.
Authors: FERD. C. VALENTINE
Journal: JAMA (1903)

[The author believes that the objects of this paper will be furthered by substituting initials for his name and by omitting his address in reprints thereof.] <h3>I. INTRODUCTORY.</h3> Many important books have been written and many valuable papers contributed to medical journals on the dangers of venereal diseases. All show that venereal diseases are more perilous to the individual, the family and the state than are all other ailments combined. Study and effort directed to their abatement lead to the inevitable conclusion that venereal diseases are due essentially to prostitution, clandestine and public. The knowledge that venereal diseases are due mainly to prostitution does not, however, reveal the means of curing the evil: 1, Because all efforts to reduce public prostitution have proven and are always likely to prove futile; 2, because clandestine prostitution is necessarily beyond all efforts to limit its still greater power for evil. The principal cause
Splenic Rupture in Infectious Mononucleosis
Authors: W. J. Gall
Journal: BMJ (1965)

When the diathermy is applied to the thorax or neck of an insulated patient the shortest electrical path is through the anaes- thetic tubing and machine or the anaesthetist, who usually has bare hands and conducting boots.When patients are intubated, the endotracheal tube is non-conducting when dry, and electrical contact is first made with the metal connector, which can easily make contact with the skin of the face but is often
Prenatal Micronutrient and Early Pregnancy Food Supplementation in Bangladesh—Reply
Authors: Lars Åke Persson, Shams Arifeen, Eva-Charlotte Ekström
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
STUDIES ON THE TOXIN PRODUCTION OF THE SHIGA BACILLI
Authors: Erik Waaler
Journal: The Journal of Experimental Medicine (1936)

1. The S, R, and Rn variants of the Shiga bacillus are equally toxic. 2. The effect of the toxin upon rabbits is the same, whether it is derived from filtrates of broth cultures (3 to 6 days old), or is obtained by autolysis of the killed bacteria, grown on agar surface. Rabbits show in both cases prostration, loss in weight, paralysis, and diarrhea. 3. When the toxin is heated to 80°C. for 1 hour, its poisonous effect nearly disappears, but its immunizing ability is unaltered. This heated toxin induces a formation of antitoxin, which can protect against the unheated toxins. 4. The anatomical changes observed in the spinal cord (degeneration of the motor neurons) and in the cecum (hyperemia and hemorrhages) are in agreement with the statements of previous authors. Furthermore, the toxin causes hyperemia and hemorrhages in the heart, hyperemia and degeneration in the kidneys and the liver.
Statistics, Smoking, and Health
Authors: John Slade
Journal: JAMA (1986)

To the Editor.—  Dr Hickey 1 suggests that tobacco use may be a manifestation of a primary hormonal deficiency relieved by nicotine. This opinion is part of a larger speculative web, namely, that tobacco use is genetically predetermined and that the people destined to use tobacco are the very people who are prone to have smaller babies and who are most likely to develop the sundry ills more commonly regarded as being caused by tobacco use. 1-3   Hickey's hypothesis provides an alternative explanation for the observation that people who use tobacco often feel more normal while smoking than immediately after stopping. The conventional interpretation of this phenomenon is that nicotine is a psychoactive drug that induces tolerance, and the abrupt cessation of tobacco use often precipitates a withdrawal syndrome. 4,5 As in alcohol or narcotic withdrawal, the newly abstinent person may feel ill and experience a temporary decrement in performance.  Mangan
“The Internist's Reading”: Literature That Illuminates Life
Authors: Edward J. Huth
Journal: Annals of Internal Medicine (1994)

Editorials1 September 1994“The Internist's Reading”: Literature That Illuminates LifeEdward J. Huth, MDEdward J. Huth, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-5-199409010-00014 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail At the center of the practice of medicine is the physician constantly engaged in the unending drama played out by patients, their families, and physicians themselves. The power of the witnessed and felt joy and pain and sadness comes in large part from the physician's being both spectator and player. But there is a limit to what the physician can perceive, having only one pair of eyes, and limits to what only one brain can digest. A wider and deeper view can come through finding what other pairs of eyes have seen. That is the value of reading literature that ... Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHumanistic Qualities in End-of-Life Care: Lessons from The Diving Bell and the Butterfly: A Memoir of Life in Death —Required Reading in an End-of-Life Care Curriculum for Internal Medicine Residents 1 September 1994Volume 121, Issue 5Page: 381KeywordsBrainLibraries ePublished: 15 August 2000 Issue Published: 1 September 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Short-Term Antimicrobial Treatment of Tuberculous Meningitis
Authors: Edwin L. Kendig, William B. Johnston
Journal: New England Journal of Medicine (1958)

TUBERCULOUS meningitis is the most serious form of tuberculous disease. Since it is generally recommended that patients with pulmonary tuberculosis receive antimicrobial therapy for at least a year,1 it naturally follows that treatment of tuberculous meningitis is carried out over a much longer period.The Committee on Therapy of the American Trudeau Society suggests that duration of treatment of tuberculous meningitis be a minimum of eighteen months to two years.2 At the Medical College of Virginia Hospital, arrangements for housing of tuberculous children have not been satisfactory. This, in addition to various economic factors, has led to early discharge of . . .
The diagnosis and management of sinusitis: A practice parameter update
Authors: Raymond G. Slavin, Sheldon L. Spector, I. Leonard Bernstein, Raymond G. Slavin, Michael A. Kaliner, David W. Kennedy, Frank S. Virant, Ellen R. Wald, David A. Khan, Joann Blessing-Moore, David M. Lang, Richard A. Nicklas, John J. Oppenheimer, Jay M. Portnoy, Diane E. Schuller, Stephen A. Tilles, Larry Borish, Robert A. Nathan, Brian A. Smart, Mark L. Vandewalker
Journal: Journal of Allergy and Clinical Immunology (2005)