tbuckley/cabot-search huggingface dataset:
Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice
Authors: Steve S. Choi, Jason K. Sicklick, Qi Ma, Liu Yang, Jiawen Huang, Yi Qi, Wei Chen, Yin-Xiong Li, Pascal J. Goldschmidt-Clermont, Anna Mae Diehl
Journal: Hepatology (2006)

Rac, a small, GTP-binding protein in the Rho family, regulates several cellular functions, including the activation of NADPH oxidase, a major intracellular producer of reactive oxygen species (ROS). Hepatic stellate cells (HSCs) isolated from mice that are genetically deficient in NADPH oxidase produce less ROS, and their activation during chronic liver injury is abrogated, resulting in decreased liver fibrosis. Therefore, we hypothesized that HSC ROS production and activation would be enhanced, and fibrosis worsened, by increasing Rac expression in HSCs. To achieve this, we used transgenic mice that express constitutively active human Rac1 under the control of the α - smooth muscle actin (α -sma ) promoter, because α -sma expression is induced spontaneously during HSC activation. Transgene expression was upregulated progressively during culture of primary Rac-transgenic HSCs, and this increased HSC ROS production as well as expression of activation markers and collagen. Similarly, Rac mice treated with carbon tetrachloride (CCl4) accumulated greater numbers of activated HSCs and had more liver damage, hepatocyte apoptosis, and liver fibrosis—as well as higher mortality—than CCl4-treated wild-type mice. In conclusion , sustained activation of Rac in HSCs perpetuates their activation and exacerbates toxin-induced liver injury and fibrosis, prompting speculation that Rac may be a therapeutic target in patients with cirrhosis.
Commissioning a national programme of research and development on the interface between primary and secondary care
Authors: J. Wisely, A. Haines
Journal: BMJ (1995)

The first call for applications to the NHS research and development programme on the interface between primary and secondary care was advertised in February 1994. A total of 674 outline proposals were submitted and 54 (8%) secured funding. Projects have been commissioned in 16 of the 21 priority areas and around 6m pounds has been committed. Analysis shows that multidisciplinary applications are more likely to be funded and that the odds for a successful application are on average nearly doubled for each discipline represented up to five. A survey of applicants and peer reviewers found satisfaction with much of the commissioning process, but peer review and feedback were subject to criticism, particularly by unsuccessful applicants. The programme shows that it is possible to commission a large number of projects in an innovative area of research and development and has identified refinements that will further increase the efficiency and acceptability of the process.
Treatment of Infections Due to Methicillin-Resistant Staphylococcus aureus
Authors: CHATRCHAI WATANAKUNAKORN
Journal: Annals of Internal Medicine (1982)

Strains of methicillin-resistant Staphylococcus aureus are resistant to other penicillins. The in-vitro susceptibility to the cephalosporins differs among strains. Some strains, susceptible to cephalosporins by the standard disk susceptibility test, are proved resistant by the quantitative dilution test; they may show pop-up colonies within the zone of inhibition when incubated further at room temperature. The clinical efficacy of the cephalosporins with or without an aminoglycoside in treating infections due to methicillin-resistant S. aureus is in doubt. To date, susceptible to vancomycin. In-vitro antagonism of vancomycin and rifampin against S. aureus has been shown. Thus, vancomycin alone appears to be the treatment of choice; if this treatment fails, aminoglycoside or rifampin should be added. Serum bactericidal titers should be carefully monitored before and after the addition of the new agent and in-vitro time-kill studies of combination of antibiotics done if feasible.
Presynaptic Ca2+ Channels Compete for Channel Type-Preferring Slots in Altered Neurotransmission Arising from Ca2+ Channelopathy
Authors: Yu-Qing Cao, Erika S. Piedras-Renterı́a, Geoffrey B. Smith, Gong Chen, Nobutoshi C. Harata, Richard W. Tsien
Journal: Neuron (2004)
Phenomenal experience and science: Separated by a “brick wall”?
Authors: Michael Pauen
Journal: Behavioral and Brain Sciences (1999)

Palmer's principled distinction between first-person experience and scientific access is called into question. First, complete color transformations of experience and memory may be undetectable even from the first-person perspective. Second, transformations of (say) pain experiences seem to be intrinsically connected to certain effects, thus giving science access to these experiences, in principle. Evidence from pain research and emotional psychology indicates that further progress can be made.
Suppression of repolarization-related arrhythmias in vitro and in vivo by low-dose potassium channel activators.
Authors: F A Fish, C Prakash, D M Roden
Journal: Circulation (1990)

Marked prolongation of cardiac action potentials and of QT intervals has been associated with early afterdepolarizations and triggered activity in vitro and with ventricular tachycardia in vivo. Because the antihypertensive potassium channel activators pinacidil and cromakalim are known to accelerate repolarization in cardiac tissues, we performed in vitro and in vivo experiments to test the hypothesis that these agents would block the arrhythmogenic effects of delayed repolarization. Early afterdepolarizations and triggered activity were elicited in canine cardiac Purkinje fibers driven at cycle lengths of 4 seconds or more (K0, 2.7 mM) during superfusion with quinidine, cesium, or sematilide, a methylsulfonylamino parasubstituted analogue of procainamide with class III antiarrhythmic activity. The potassium channel activators invariably (17 of 17) abolished this form of abnormal automaticity. This effect was observed at low concentrations that did not alter action potential characteristics at shorter cycle lengths. Intravenous Cs+ (total dose, 4.5 mM/kg) was used to produce ventricular arrhythmias in anesthetized rabbits randomly pretreated in a double-blind fashion with either low-dose pinacidil (0.2 mg/kg) or vehicle. Pinacidil pretreatment resulted in significantly fewer total ventricular ectopic beats (168 +/- 157 versus 582 +/- 448, p less than 0.005) and episodes of ventricular tachycardia (four of nine versus nine of nine, p = 0.057). At this dose, pinacidil did not alter mean blood pressure before Cs+ and maximal hypertensive response after Cs+. In summary, the potassium channel activators pinacidil and cromakalim suppressed triggered activity related to prolonged repolarization at concentrations that did not affect action potential characteristics at normal rates in vitro; pinacidil blunted arrhythmias produced by cesium administration in vivo without lowering blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Experimental Small-Artery Grafts in Dogs Treated with Immunosuppressive Drugs
Authors: C. M. Vickery, H. L. McCombs, R. Warren
Journal: New England Journal of Medicine (1965)

THIS study has been an attempt to modify the degeneration of fresh arterial homografts using the dog's femoral artery by treatment of the recipient animal with modern immunosuppressive drugs.The use of homografts for peripheral arterial replacement and bypass has been abandoned because of the high incidence of poor long-term results,1 2 3 which are to a large extent attributable to the inevitable degenerative changes that occur with time. In contrast, experimental work has amply confirmed that fresh autogenous arterial tissue undergoes little appreciable long-term change and heals as a living structure with retention of a practically normal histologic appearance.4 5 6 7 8 9 The facetious . . .
Pancreatic Transplants: New Wrinkles
Authors: Henry T. Ricketts
Journal: JAMA (1974)

The discovery of insulin by Banting and Best some 50 years ago was an unmitigated blessing, almost a miracle, for thousands of diabetics who would have died without it. During this half century, however, it has been recognized that injections of the beneficient fluid fall short of being the ultimate treatment. Not only are syringes and needles an onerous nuisance, but insulin, which certainly prolongs life, has failed to prevent premature deaths from vascular disease,<i>perhaps</i>because its intermittent administration cannot mimic the on and off response to physiologic demand that the pancreas provides. In these circumstances, it was logical to consider transplanting the pancreas into insulin-requiring diabetic patients. Attempts made in animals, however, beginning more than 20 years ago, met with little success. With the advent of immunosuppressive agents, the bold were further emboldened to perform the operation on human subjects. The latest available data<sup>1</sup>show that, by
Expansion of CD8+ T cells lacking Sema4D/CD100 during HIV-1 infection identifies a subset of T cells with decreased functional capacity
Authors: Emily M. Eriksson, Jeffrey M. Milush, Emily L. Ho, Mariana D. Batista, Sara J. Holditch, Chris E. Keh, Philip J. Norris, Sheila M. Keating, Steven G. Deeks, Peter W. Hunt, Jeffrey N. Martin, Michael G. Rosenberg, Frederick M. Hecht, Douglas F. Nixon
Journal: Blood (2011)
Bone disease in predialysis, hemodialysis, and CAPD patients: Evidence of a better bone response to PTH
Authors: Armando Torres, Victor Lorenzo, Domingo Hernández, José C. Rodríguez, María Teresa Concepción, Aurelío P. Rodríguez, Alexis Hernández, Eduardo de Bonis, Ernesto Darias, José M. González-Posada, Manuel Losada, Margarita Rufino, Arnold J. Felsenfeld, Mariano Rodríguez
Journal: Kidney International (1995)
Myocardial fatty acid imaging identifies a group of hemodialysis patients at high risk for cardiac death after coronary revascularization
Authors: Masato Nishimura, Toshiko Tokoro, Masasya Nishida, Tetsuya Hashimoto, Hiroyuki Kobayashi, Satoru Yamazaki, Ryo Imai, Koji Okino, Hakuo Takahashi, Toshihiko Ono
Journal: Kidney International (2008)
Familial Hyperparathyroidism
Authors: RICHARD E. GOLDSMITH
Journal: Annals of Internal Medicine (1976)

Sixty-nine out of a kindred of 100 members covering five generations were examined and studied, and 34 were hypercalcemic. Sixteen subjects were believed, on the basis of laboratory and clinical observations, to have primary hyperparathyroidism. Eight patients were subjected to exhaustive study to identify polyendocrine involvement before neck exploration. No coexisting endocrine abnormalities were found; operation showed multiparathyroid gland involvement in most instances. Measurement of immunoassayable calcitonin and assessment of renal and gut function were carried out in 37 subjects to search out possible causes of "reactive" parathyroid gland hyperfunction. While no such cause-effect relationship was noted for this kindred, 16 of the subjects so tested had serum calcitonin content below the assay limits of sensitivity. What role this apparent lack of calcitonin played in the development of hyperparathyroidism (or vice versa) needs clarification.
New evidence linking salt and hypertension.
Authors: R Finn
Journal: BMJ (1981)

The paper discusses the current medical practice of ‘gender verification’ in sports from an ethical point of view. It takes the recent public discussion about 800 m runner Caster Semenya as a starting point. At the World Championships in Athletics 2009 in Berlin, Germany, Semenya was challenged by competitors as being a so called ‘sex impostor’. A medical examination to verify her sex ensued. The author analyses whether athletes like Semenya could claim a right not to know that is generally acknowledged in human genetics and enforced by international and national genetic privacy laws. The relevance of this right for genetic diagnosis in sports is discussed. To this end, the interests of the athlete concerned and of third parties are balanced according to the expected benefits and harms.Harm is documented in a number of cases and includes unjustified disqualification, severe sex and gender identity crisis, demeaning reactions, social isolation, depression and suicide. Benefits are dubious as most cases of intersex are considered irrelevant for sports competition. It has to be concluded that the benefits to be gained from ‘gender verification’ in sports via genetic testing do not outweigh the grave individual disadvantages. The current practice of athletic associations to largely ignore the right of competitors not to know does not comply with prevailing ethical provisions on the protection of sensitive personal data. Therefore, genetic ‘gender verification’ in sports should be abolished.
Abstract 2722: Transcription factor NF-kB in esophageal squamous cell carcinoma: Alterations in activity and expression during Human Papillomavirus infection
Authors: Showket Hussain, Neha Singh, Irfana Salam, Mohammad A. Bhat, Nandita Kakkar, Mohammad M. Mir, Mushtaq A. Siddiqi, Seemi F. Basir, Alok C. Bharti, Mausumi Bharadwaj, Bhudev C. Das
Journal: Cancer Research (2011)

Abstract Background: Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related deaths in Jammu and Kashmir (J&amp;K) region of India. A substantial proportion of esophageal carcinoma is associated with infection of high risk HPV type 16 and HPV18, the oncogenic expression of which is controlled by host cell transcription factor Nuclear factor kappa B (NF-kB). We therefore have investigated the role of DNA binding and expression pattern of NF-kB in esophageal cancer with or without HPV infection. Methods: Seventy five histopathologically-confirmed esophageal cancer and an equal number of corresponding adjacent normal tissue biopsies from Kashmir were analyzed for HPV infection, DNA binding activity and expression of NF-kB family of proteins by PCR, gel shift assay and immunoblotting respectively. Results: A high DNA binding activity and elevated expression of NF-kB proteins was observed in esophageal cancer tissue biopsies whereas, it was undetectable or reduced in all corresponding normal adjacent tissues but did not differ with respect to different grades of ESCC. In order to examine the composition of functional NF-kB complex both in HPV positive and negative esophageal tumors gel supershift assays were performed by adding specific antibodies to all 5 members of NF-kB family proteins (p50, p52, p65, RelB, and cRel). Supershift analysis revealed that p50 was a major binding partner and showed a preferential homodimerization in HPV negative esophageal tumors (61/75) and this participation was more evident in advanced grade of the disease (MDSCC+PDSCC; 46/61). On the other hand, HPV16 infected tumor tissues (n=14) showed hetrodimerization between p50 and cRel in more than 85% (12/14) of esophageal tumors. Interestingly, 2 cases with HPV infection p65 was also found to participate along with p50 and cRel in well-differentiated state of esophageal cancer. It is quite likely that the functional NF-kB complex formation in advanced grade of esophageal cancer comprises of p50/p50 homodimerization whereas in HPV infected esophageal tumors p50/cRel hetrodimerization occurs along with p65 in well differentiated state of the disease. Conclusion: Differential NF-kB dimerization and expression of its specific proteins between HPV – positive and HPV – negative cases indicate that NF-kB may play an important role during HPV induced esophageal carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2722. doi:10.1158/1538-7445.AM2011-2722
BCR-ABL1 doubling times more reliably assess the dynamics of CML relapse compared with the BCR-ABL1 fold rise: implications for monitoring and management
Authors: Susan Branford, David T. Yeung, Jodi A. Prime, Soo-Young Choi, Ju-hee Bang, Jin Eok Park, Dong-Wook Kim, David M. Ross, Timothy P. Hughes
Journal: Blood (2012)
Iron in Multivitamin Supplements
Authors: David E. Langdon
Journal: Annals of Internal Medicine (1999)

Letters20 July 1999Iron in Multivitamin SupplementsDavid E. Langdon, MDDavid E. Langdon, MDArlington, TX 76015 (Langdon)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-2-199907200-00026 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The superb supplement on iron overload (1) didn't mention the impact of our current vogue for nutritional supplements. At risk from iron supplements are not only the possibly 1 million persons with potential hemochromatosis but also the elderly (if not losing blood through menstruation or blood donations), in whom an iron deficiency state may be the only clue to a potentially fatal, still curable, bleeding gut lesion. Most large pharmacies aren't stocking adult multivitamins without “minerals” because they no longer sell! Walgreen's “best-selling” multivitamin-mineral combination has 25 mg of iron. The hemochromatosis patient's super-absorbing gastrointestinal tract would ...Reference1. Iron Overload, Public Health, and Genetics. Ann Intern Med. 1998; 129:921-96. Google Scholar Author, Article, and Disclosure InformationAuthors: David E. Langdon, MDAffiliations: Arlington, TX 76015 (Langdon) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 20 July 1999Volume 131, Issue 2Page: 158KeywordsBloodBlood banksGastrointestinal tractGeneticsHemochromatosisHemorrhageIron deficiencyLesionsNutritionWine ePublished: 15 August 2000 Issue Published: 20 July 1999 Copyright & PermissionsCopyright © 1999 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
AUTOIMMUNE VERSUS AUTOSEROLOGIC
Authors: M. DAVID POSNER
Journal: Annals of Internal Medicine (1967)

Letters and Comments1 December 1967AUTOIMMUNE VERSUS AUTOSEROLOGICM. DAVID POSNER, M.D.M. DAVID POSNER, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-67-6-1350_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editor: This letter is in reference to the following article: EYSTER, M. E.: Melphalan (Alkeran®) erythrocyte agglutinin and hemolytic anemia. Ann. Intern. Med. 66: 573, 1967.The designation "autoimmune" disease has been applied to a large number of disease entities, all of which have in common the fact that endogenous protein molecule combines with host tissue. This fact, however, as I have related it, does not distinguish between autoimmune and what might be termed autoserologic states. The distinguishing characteristic of the immune state is that endogenous protein production is "stimulated"—in direct response to the presence of antigen. Admittedly,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 3281 Wendy Way, Los Alamitos, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByThe Importance of Fault in Contract Law 1 December 1967Volume 67, Issue 6Page: 1350-1350KeywordsAgglutininsAntigensAutoimmune diseasesHemolytic anemiaImmune responseProteins Issue Published: 1 December 1967 PDF DownloadLoading ...
A Mother in Haiti
Authors: Michelle Daniel
Journal: Annals of Internal Medicine (2010)

On Being a Doctor19 October 2010A Mother in HaitiMichelle Daniel, MDMichelle Daniel, MDFrom Rhode Island Hospital, Providence, RI 02903.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-153-8-201010190-00015 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Women wear many hats. Two of mine are physician and mother. On most days, these roles are very separate, but at times the boundaries blur. My most difficult moments as a physician arise when, mother to mother, I must tell a woman that her child has died. Fortunately, as a physician in the United States, I do not have to do this every day.I am the mother of 2 beautiful girls whose health and circumstances I often take for granted. I met their father 12 years ago while working in Haiti. Tears streamed down their faces as first daddy, ... Author, Article, and Disclosure InformationAffiliations: From Rhode Island Hospital, Providence, RI 02903.Corresponding Author: Michelle Daniel, MD, Rhode Island Hospital, 593 Eddy Street, Claverick Building, Second Floor, Providence, RI 02903; e-mail, [email protected]com. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 October 2010Volume 153, Issue 8Page: 546KeywordsChildrenEmotionsKneesMemoryMouthResuscitationSleepTaxesTetanusTongue ePublished: 19 October 2010 Issue Published: 19 October 2010 Copyright & PermissionsCopyright © 2010 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Arthur L Rosenbaum
Authors: N. Stafford
Journal: BMJ (2010)

Innovative paediatric eye surgeon and target of animal rights extremists



Arthur Rosenbaum discovered a plastic container of orange coloured liquid beneath his BMW parked in front of his Los Angeles house on the morning of Sunday 24 June 2007. A rag was dangling from a small opening of a container next to a matchbook, with a half smoked cigarette inserted through the matches.

Rosenbaum, a paediatric ophthalmologist at the University of California in Los Angeles (UCLA) well known for developing innovative surgical techniques for eye muscle disorders and who had treated more than 10 000 children in his 36 years at UCLA, telephoned the police. Bomb experts said that the container was an “incendiary device that, had the fuse not failed to light, was powerful enough to have destroyed the auto.” Anti-animal research extremists claimed responsibility, stating that Rosenbaum had been targeted because of “vile and evil things he does to primates at UCLA.”

Rosenbaum had become a target of extremists despite having ties to only one animal research project, a pilot study testing electrical stimulation on primates to revitalise paralysed eye muscles and correct severe cross eyed conditions. In subsequent months he was repeatedly threatened and harassed. Masked activists …
Management of Pharyngeal Carriers of Group A Streptococcal Organisms-Reply
Authors: Robert F. Perry, Matthew T. Maher
Journal: JAMA (1997)

<h3>In Reply.</h3> —In our study, we reported that a highly virulent group A streptococcal clone (PFGE-1) caused multiple cases of invasive streptococcal disease in a small community from January through March 1995. Fifty-nine (32%) of 187 children attending the only elementary school in this community carried group A streptococcus organisms in their throats, and in 46 (78%) of the 59 carriers, the PFGE-1 clone was isolated. All 59 children who carried group A streptococcus were offered antimicrobial therapy, and all were treated. No additional cases of invasive disease caused by the PFGE-1 clone occurred in this community at the conclusion of this intervention. However, no follow-up pharyngeal cultures were performed to determine whether the prevalence of the PFGE-1 among these carriers decreased following antimicrobial therapy. Even if one assumes an eradication rate among the PFGE-1 streptococcal carriers in our study similar to that reported by Drs Perry and Maher (83%), other factors