tbuckley/cabot-search huggingface dataset:
Loss of Cytochrome P450 17A1 Protein Expression in a 17α-Hydroxylase/17,20-Lyase-Deficient 46,XY Female Caused by Two Novel Mutations in the CYP17A1 Gene
Authors: Nayelli Nájera, Nayely Garibay, Yadira Pastrana, Icela Palma, Yolanda-Rocio Peña, Javier Pérez, Ninel Coyote, Alberto Hidalgo, Susana Kofman-Alfaro, Gloria Queipo
Journal: Endocrine Pathology (2009)
Radiobiology for the Radiologist
Authors: Walter G. Gunn
Journal: JAMA (1988)

"Doctor, if I have this mammogram you've recommended, what are my chances of getting cancer at a later date from the irradiation?" "What will the radiation from this CT scan do to my fetus in case I'm pregnant?" "I'm an operating room nurse of childbearing age. Will radiation from portable x-rays in the OR damage my ovaries?" "I've had radiations for cancer before. If I get these dental x-rays, will that increase the risk to me? Will the benefit be worth the risk?" In the newest edition of what has become a classic radiation biology text, Dr Eric Hall devotes about one fourth of the total to the background data and literature that lets us answer such questions, questions that in the same or a similar form have been addressed to almost all physicians. This background is readable and presented in orderly fashion. He makes it, above all,<i>encompassable</i>in
Percutaneous Balloon Aortic Valvuloplasty for Aortic Stenosis in Elderly Patients at High Risk for Surgery
Authors: JOHN F. SCHNEIDER
Journal: Annals of Internal Medicine (1987)

Six elderly patients had percutaneous balloon aortic valvuloplasty for severe, symptomatic calcific aortic stenosis because valve replacement surgery was considered too risky in five patients with severe coexisting cardiac or other medical problems and because one patient refused to have surgery. The procedure resulted in a significant reduction in the mean (± SD) aortic valve gradient, from 47 ± 13 to 32 ± 12 mm Hg (change, - 32%,p < 0.01), and a significant increase in the mean area of the aortic valve, from 0.64 ± 0.12 to 0.90 ± 0.17 cm2 (change, + 40%, p < 0.001). Blood loss from the femoral puncture site was the only major procedural complication. At a mean follow-up of 2 months after the procedure, all patients were alive and dyspnea had improved by two New York Heart Association functional classes in four patients and by one functional class in two patients. A significant short-term increase in aortic valve area and alleviation in symptoms can be achieved safely by percutaneous balloon aortic valvuloplasty in elderly patients with severe calcific aortic stenosis who are at high risk for surgical complications.
Approaches for assessing health risks from complex mixtures in indoor air: a panel overview.
Authors: C J Henry, L Fishbein, W J Meggs, N A Ashford, P A Schulte, H Anderson, J S Osborne, D W Sepkovic
Journal: Environmental Health Perspectives (1991)

Critical to a more definitive human health assessment of the potential health risks from exposure to complex mixtures in indoor air is the need for a more definitive clinical measure and etiology of the health effects of complex mixtures. This panel overview highlights six of the eight presentations of the conference panel discussion and features a number of the major topical areas of indoor air concern. W. G. Meggs assessed clinical research priorities with primary focus on the role of volatile organic chemicals in human health, recognizing the areas where definitive data are lacking. By recognizing many types of chemical sensitivity, it may be possible to design studies that can illuminate the mechanisms by which chemical exposure may cause disease. The critically important topic of multiple chemical sensitivity was discussed by N. A. Ashford, who identified four high risk groups and defined the demographics of these groups. P. A. Schulte addressed the issue of biological markers of susceptibility with specific considerations of both methodological and societal aspects that may be operative in the ability to detect innate or inborne differences between individuals and populations. Three case studies were reviewed. H. Anderson discussed the past and present priorities from a public health perspective, focusing on those issues dealing with exposures to environmental tobacco smoke and formaldehyde off-gassing from materials used in mobile home construction. J. J. Osborne described several case studies involving wood smoke exposure to children, with emphasis on the significantly greater occurrence of chronic respiratory symptoms and acute chest illness for children from homes heated with woodburning stoves.(ABSTRACT TRUNCATED AT 250 WORDS)
THE OPERATIVE TREATMENT OF SIMPLE FRACTURES
Authors: A. F. JONAS
Journal: JAMA (1910)

The treatment of simple fractures by the open operative procedure has gained much in favor during the last few years. In spite of the fact that surgeons have occupied themselves much in the study of this branch of surgery, perfection has not been attained and the controversy still continues. Among practical surgeons of large experience direct fixation appliances in compound fractures, where the bones are exposed, when they cannot be kept in position by splints, have come into general use. There seems to be a general unanimity of opinion that such is the best practice. But when the matter of simple fractures is presented for consideration there is a lack of uniform opinion.  In this connection I shall draw from my own personal experience, gathered from a rather extensive service of accident surgery, extending over a period of upwards of twenty-five years. There will be no tabulation of cases and
Abstract 2482A: ARHI (DIRAS3) downregulates Ras-MAPK signaling and inhibits transformation of NIH3T3 cells through direct interaction with GTP-bound Ras
Authors: Margie N. Sutton
Journal: Cancer Research (2014)

Abstract Somatic mutation of Ras was the first genetic alteration documented to drive human oncogenesis. Activating mutations of H-Ras, N-Ras, or K-Ras are associated with 30% of all human cancers. Characterization of wild type Ras proteins has identified their essential role in intra-cellular signaling networks controlling cell proliferation, differentiation and survival. Despite intensive efforts, effective targeted therapy directed against mutated Ras has remained elusive. Regulation of Ras function has been studied in depth, but relatively little attention has been paid to physiological inhibitors of Ras. Our group has previously reported that the maternally imprinted Ras-related tumor suppressor gene ARHI (DIRAS3) is downregulated in more than 60% of ovarian cancers and several other tumor types. Re-expression of ARHI at physiologic levels can inhibit ovarian cancer cell proliferation, block migration, induce autophagy, mediate tumor dormancy and block both PI3K and Ras-MAPK signaling. ARHI shares 50-60% homology with the H- and K-Ras genes, differing primarily in a 34-amino acid N-terminal extension that is required for most of ARHI's functions. The mechanism by which ARHI regulates Ras-MAPK signaling is not fully understood. Here, we show that re-expression of ARHI in NIH3T3 murine fibroblasts inhibits cell proliferation, suppresses clonogenic growth and blocks cell transformation by constitutively active mutant H-Ras. Addition of the N-terminal extension of ARHI to mutant H-Ras also prevents malignant transformation. ARHI interacts directly with mutated Ras on co-immunoprecipitation and can inhibit GTP-bound Ras activity following overexpression of the constitutively active construct. We hypothesize that inhibition of the Ras-MAPK signaling pathways following re-expression of ARHI (DIRAS3) may be, in part, the effect of a direct interaction between GTP-bound Ras and ARHI, resulting in the restoration of intrinsic Ras GTPase activity. Our results suggest that ARHI (DIRAS3) may serve as a novel inhibitor of activated Ras, and re-expression of ARHI in tumors exhibiting an oncogenic mutation of Ras might permit more specifically targeted therapy. Citation Format: Margie N. Sutton. ARHI (DIRAS3) downregulates Ras-MAPK signaling and inhibits transformation of NIH3T3 cells through direct interaction with GTP-bound Ras. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2482A. doi:10.1158/1538-7445.AM2014-2482A
Making the prices of new drugs fairer
Authors: Julio Sotelo
Journal: BMJ (2007)

The prices of novel drugs are spiralling, and the rises seem impossible to contain. Drugs are fast becoming unaffordable for many patients and public healthcare institutions, even in rich countries. This is a huge challenge for medical institutions and governments; the problem is so great nowadays that several countries consider it a matter of national security. 

Several chronic diseases (among them epilepsy, arthritis, diabetes, hypertension, and depression) require lifelong treatment, an economic burden that many patients find almost impossible to meet. The impressive success of biomedical research in recent decades in curing and controlling countless diseases is increasingly eclipsed by the rising costs of all new treatments, even those for simple or self limiting disorders.

The cost of biomedical research that eventually results in new drugs is almost entirely supported by public institutions without commercial interests. Only the final steps in the design and testing of a new drug rest with the drug companies, which use the enormous amount of scientific information generously created by the biomedical research community without giving much back. Although nothing is wrong with such a sequence of events, in the case of new drugs various oddities in the way they are commercialised and marketed are of dubious morality, even if legally correct.

By way of practical comparison, consider the development of a highly successful device, a product of scientific and technological research …
Superblindsight, Inverse Anton, and tweaking A-consciousness further
Authors: Oliver Kauffmann
Journal: Behavioral and Brain Sciences (2004)

It is argued that Block's thought experiment on superblindsight and "the Inverse Anton's syndrome" are not cases of A-consciousness without P-consciousness. "Weak dispositional states" should be excluded from the set of A-conscious states, and a subject's being reflectively conscious of a P-conscious state is suggested as a better candidate for A-consciousness. It is further pointed out that dreams, according to Block's own criterion but contrary to what he claims, are A-unconscious and it is argued that Block should not accept the idea that high-information representational content is an empirically sufficient condition of phenomenality in human beings.
Abstract 1860: Protective effect of catechol-O-methyltransferase-mediated 4-hydroxyestradiol metabolism in human renal cell cancers
Authors: Inik Chang, Jan Liu, Shahana Majid, Sharanjot Saini, Mohd S. Zaman, Soichiro Yamamura, Vary Shahryari, Takeshi Chiyomaru, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka
Journal: Cancer Research (2012)

Abstract Long-term exposure to estrogen and its metabolites may play an important role in renal cell carcinogenesis. Catechol-O-methyltransferase (COMT) participates in the estrogen metabolism pathway by neutralizing toxic substances. Although reduced COMT activity has been suggested to be a risk factor for estrogen-associated cancers, no studies have investigated the biological significance of COMT in the pathogenesis of human renal cell cancers (RCC). Using quantitative PCR, Western blotting and immunohistochemical staining, we initially found that COMT levels are significantly decreased in human RCC tissues and cells suggesting a suppressive role of COMT in tumor development. However, transient over-expression of COMT has no effect on the proliferation, apoptosis and cell cycle progression of RCC cell lines. In contrast, when cells over-expressing COMT are treated with its substrate 4-hydroxyestradiol (4-OHE2), growth is inhibited by apoptotic cell death. We also found that COMT over-expression combined with 4-OHE2 induces up-regulation of growth arrest- and DNA damage-inducible protein ≤ (GADD45α). We further show that down-regulation of GADD45α by a siRNA-mediated approach inhibits cell death, indicating the essential role of GADD45α in the underlying mechanism of COMT action in response to 4-OHE2. Finally, 4-methoxyestradiol (4-ME) fully reproduces the anti-proliferative function of COMT with 4-OHE2 by promoting GADD45α induction. Together, our study shows that COMT in the presence of 4-OHE2 prevents RCC cell proliferation by enhancing apoptosis, and that GADD45α plays a critical role in the COMT-mediated inhibition of RCC. These findings will provide new direction for the biomarker detection and corresponding treatment in the prevention of human RCC. 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 1860. doi:1538-7445.AM2012-1860
On the Value of Paracentesis of the Chest in the Treatment of Pleuritic Effusion
Authors: H. Barnes
Journal: BMJ (1877)

25 and 75 per cent.; for purulent transformations, 45 and 55 per cent.; and for cases of which no account is given (and in which, in this analysis, I have taken as uncomplicated), 33 and 66 per cent.respec- tively.The difference in the frequency of phthisis and purulent trans- formation is scarcely sufficiently considerable to be made the basis of any special deduction, though, ai priori, the former might have been expected to be less frequent and the latter more frequent, compara- tively, after the age of thirty.The bulk of the cases in which the greater preponderant mortality depends after thirty appears, therefore, firstly, in the greater number of general grave complications which were present after this age; and secondly, among unexplained causes of death; the latter showing an inherent tendency to a greater fatality of the operation in more advanced periods of life, into which, however, on the data at present existing, it does not seem possible to pursue this inquiry further.
Effects of lidocaine on relation between defibrillation threshold and upper limit of vulnerability in open-chest dogs.
Authors: S L Topham, Y M Cha, B B Peters, P S Chen
Journal: Circulation (1992)

BACKGROUND The purpose of the present study was to test the effects of lidocaine on the relation between the defibrillation threshold and the upper limit of vulnerability. METHODS AND RESULTS The shock strength associated with a 50% probability of successful defibrillation (DFT50) and the shock strength associated with a 50% probability of reaching the upper limit of vulnerability (ULV50) were determined in 11 open-chest dogs by using the delayed up-down method before and during lidocaine (seven dogs) or normal saline (four dogs) infusion. The ventricles were paced at a cycle length of 300 msec. Shocks of various strengths were then given via a patch-patch electrode configuration on the anterior and posterior surfaces of the ventricle to determine the ULV50. Once ventricular fibrillation was induced, shocks were given 15-20 seconds later via the same electrode configuration to determine the DFT50. Lidocaine infusion resulted in a serum level of 15 +/- 4 micrograms/ml. This was associated with a lengthening of the QT interval but not with the widening of the QRS complex. In all dogs, both the ULV50 and the DFT50 increased significantly when tested during lidocaine infusion. Mean ULV50 during lidocaine infusion was 496 +/- 70 V or 13.1 +/- 4.3 J, which were significantly higher than the baseline values of 333 +/- 67 V or 5.3 +/- 2.2 J (p less than 0.001 for both voltage and energy). Mean DFT50 during lidocaine infusion was 407 +/- 41 V or 8.7 +/- 1.7 J, which were significantly higher than the baseline values of 300 +/- 38 V and 4.4 +/- 1.1 J (p = 0.004 for voltage and p = 0.013 for energy). The r values between the ULV50 and the DFT50 were 0.79 (p = 0.037) for voltage and 0.80 (p = 0.030) for energy at baseline and 0.85 (p = 0.016) for voltage and 0.88 (p = 0.009) for energy during the lidocaine infusion. However, the increments of the ULV50 (163 +/- 88 V or 7.8 +/- 4.6 J) were significantly greater than the increments of the DFT50 (107 +/- 51 V or 4.4 +/- 1.9 J, p = 0.035 for voltage and p = 0.023 for energy). Normal saline infusion did not alter DFT50 or ULV50. CONCLUSIONS Lidocaine infusion significantly increases both ULV50 and DFT50. These results are compatible with the upper limit of vulnerability hypothesis of defibrillation. However, the greater increase of the upper limit of vulnerability than the defibrillation threshold with lidocaine infusion indicates that other factors may also need to be considered to explain the results.
The hospice movement
Authors: J. P. Callan
Journal: JAMA (1979)

Transition from life to death is terrifying. It demonstrates with grim finality man's time-limited existence. Dying is a distressing journey beyond the frontiers of human knowledge and experience, and nothing generates greater fear than the unknown. Thus, it is not surprising that dying arouses strong emotions in the deceased before death and in the bereaved afterward.  While man's technical skills have enabled him to postpone the inevitable, eventually he must bow to the agony of extinction, which meets him sometimes on the road, sometimes at home, and often in the hospital. To facilitate and succor this process, special hospices have been founded across our country. The idea of hospice, however, is not new. It has its roots in medieval monasteries and convents. In modern times Our Ladies Hospice has been functioning in Dublin for almost 100 years.  The movement's current impetus in the United States started when the National Cancer
Early and non-reversible decrease of CD161++/mucosal associated invariant T cells in HIV infection
Authors: Cormac Cosgrove, James E. Ussher, Andri Rauch, Kathleen Gärtner, Ayako Kurioka, Michael H. Hühn, Krista Adelmann, Yu-Hoi Kang, Joannah R. Fergusson, Peter Simmonds, Philip Goulder, Ted H. Hansen, Julie Fox, Huldrych F. Günthard, Nina Khanna, Fiona Powrie, Alan Steel, Brian Gazzard, Rodney E. Phillips, John Frater, Holm Uhlig, Paul Klenerman
Journal: Journal of Infection (2013)
Infection with a Chlorophyllic Eukaryote after a Traumatic Freshwater Injury
Authors: Lars F Westblade, Sangeetha Ranganath, William Michael Dunne, Carey-Ann D Burnham, Robert Fader, Bradley A Ford
Journal: New England Journal of Medicine (2015)

Infections with chlorophyllic algae are uncommon. Invasive infection with Desmodesmus armatus developed in two patients independently after they each sustained a penetrating freshwater injury.
Cutaneous Human Papillomaviruses Down-regulate AKT1, whereas AKT2 Up-regulation and Activation Associates with Tumors
Authors: Ryan F.L. O'Shaughnessy, Baki Akgũl, Alan Storey, Herbert Pfister, Catherine A. Harwood, Carolyn Byrne
Journal: Cancer Research (2007)

Abstract Epithelial tumorigenesis has been linked to AKT up-regulation. Human papillomaviruses (HPV) cause anogenital cancers and anogenital HPV infection up-regulates AKT activity. Mounting evidence points to a role for cutaneous HPVs as etiologic factors in skin tumorigenesis. High-risk cutaneous β HPVs have been linked to carcinogenesis in immunosuppressed patients, and high-risk cutaneous HPV8 genes enhance tumorigenesis in transgenic mice. We find that, in contrast to anogenital HPVs, cutaneous HPV8 early genes down-regulate epidermal AKT activity by down-regulating AKT1 isoform levels. This down-regulation occurs before papilloma formation or tumorigenesis and leads to cutaneous differentiation changes that may weaken the epidermal squame for viral release. We find that, in viral warts (papillomas) and HPV gene-induced epidermal tumors, AKT activity can be activated focally by up-regulation and phosphorylation of the AKT2 isoform. In squamous cell carcinomas (SCC), AKT1 down-regulation is also common, consistent with a viral influence, whereas AKT2 up-regulation is widespread. Activation of up-regulated AKT2 by serine phosphorylation associates with high-grade tumors. Our data suggest that AKT2 up-regulation is characteristic of SCC and that coincident AKT2 activation through serine phosphorylation correlates with malignancy. These findings highlight differences between the effects of anogenital and cutaneous HPV on epithelial AKT activity and furthermore show that AKT isoforms can behave differently during epidermal tumorigenesis. These findings also suggest AKT2 as a possible therapeutic tumor target in SCC. [Cancer Res 2007;67(17):8207–15]
Topical therapies for the treatment of localized plaque psoriasis in primary care: a cost-effectiveness analysis
Authors: L. Sawyer, E.J. Samarasekera, D. Wonderling, C.H. Smith
Journal: British Journal of Dermatology (2013)

Topical therapies are a mainstay of psoriasis treatment, but they vary substantially in terms of cost.To determine the cost-effectiveness and optimal treatment sequence for psoriasis of the trunk, limbs and scalp.Probabilities of response from a network meta-analysis were used to determine the short-term efficacy of topical therapies. Longer-term outcomes, including relapse, were informed by published evidence and clinical opinion. Benefits of treatment were measured as quality-adjusted life years (QALYs). Direct costs included topical agents, primary and secondary care visits and second-line therapies for treatment failures.For the trunk and limbs, initial treatment with a two-compound formulation (TCF) product containing vitamin D and potent corticosteroid provided the most QALYs, followed by separate morning and evening application of vitamin D and potent corticosteroid [two-compound application, TCA (am/pm)], and then twice-daily potent corticosteroids. The use of twice-daily potent corticosteroids was the most cost-effective first-line strategy (incremental cost-effectiveness ratio £ 20,000 per QALY), followed by TCA (am/pm) (£ 22,658 per QALY) and TCF product (£ 179,439 per QALY). For scalp psoriasis, initial treatment with very potent corticosteroids generated the most QALYs, followed by TCF product and then potent corticosteroids. Very potent corticosteroids were the most cost-effective treatment but, if too aggressive, potent corticosteroids were optimal followed by TCF product (£ 219,846 per QALY). The cost-effectiveness of second- and third-line topical agents varied with the assumptions made.Potent corticosteroids, used alone or in combination with vitamin D, are the most cost-effective treatment for patients with psoriasis of the trunk and limbs. Potent or very potent corticosteroids are the most cost-effective treatment for patients with scalp psoriasis.