tbuckley/cabot-search huggingface dataset:
Abstract 5603: Minocycline abrogates IL-6 signaling and inhibits migration, invasion and adhesion capacity of ovarian cancer cells.
Authors: Parvin Ataie-Kachoie, David L. Morris, Mohammad H. Pourgholami
Journal: Cancer Research (2013)

Abstract Aims: Minocycline (7-dimethylamino-6-desoxytertracycline) has been recognized as a drug with interesting pleiotropic properties including suppression of pro-inflammatory cytokine levels. The beneficial effects of minocycline arisen from suppression of proinflammatory cytokines and in particular IL-6 have been elucidated in central nervous system. However, this drug has never been examined in cancers with aberrant IL-6 expression. Considering the key role of IL-6 and its signaling pathways in the growth and progression of ovarian cancer, we evaluated whether minocycline modulates IL-6, its receptor system and signaling pathways in ovarian cancer. Methods: Expression of IL-6 in control and minocycline-treated ovarian cancer cell lines (OVCAR-3, SKOV-3 and CAOV-3) was determined by immunocytochemistry. ELISA was used to quantify the effects of minocycline on both constitutive and IL-1β or 4-OH-estradiol stimulated IL-6 expression in these cell lines. The effects of minocycline on IL-6R expression was assessed by immunocytochemistry and western blot. Activation of STAT3 and ERK1/2, two major pathways down-stream of IL-6 were evaluated by western blotting. To further characterize the influence of minocycline against IL-6 bioactivity, the effect of the drug on the functional status of SKOV-3 cells was examined by adhesion assay and transwell migration and invasion assay. Finally, to determine the effect of minocycline on IL-6 expression in vivo, female nude mice bearing intraperitoneal OVCAR-3 tumors were treated with a single 30 mg/kg dose of minocycline administered intraperitoneally for 4 and 24 h. The IL-6 expression in plasma and tumor samples excised from these animals was evaluated by ELISA and western blot. Results: We found that minocycline was potent in suppressing both constitutive and stimulated IL-6 expression in vitro. Analysis of plasma and tumors also revealed substantial down-regulation of IL-6 in minocycline-treated mice in vivo. Moreover, minocycline blocked the expression of IL-6R and phosphorylation of STAT3 and ERK1/2 time-dependently. It was also found that minocycline-treated cells exhibit dose-dependent attenuation of cell adhesion, migration and invasion capacity. Conclusion: These results demonstrated that minocycline effectively blocks IL-6 signaling in ovarian cancer. Blockage of IL-6 signaling may provide benefits for the treatment of this deadly cancer. Citation Format: Parvin Ataie-Kachoie, David L. Morris, Mohammad H. Pourgholami. Minocycline abrogates IL-6 signaling and inhibits migration, invasion and adhesion capacity of ovarian cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5603. doi:10.1158/1538-7445.AM2013-5603
ACP Practice Guidelines
Authors: Richard Bettigole
Journal: Annals of Internal Medicine (1992)

Letters1 August 1992ACP Practice GuidelinesRichard Bettigole, MDRichard Bettigole, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-117-3-268_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the Editors:When they are good, practice guidelines issued by organizations like the American College of Physicians (ACP) may well be very, very good, but when they are bad, they will, like the little girl in the nursery rhyme, be horrid. The assertion that such guidelines "should become the preferred source for definitive advice" (1) ignores the fact that, because data accumulate continuously, any such guidelines would potentially be outdated before publication. The assertion is also based on a false premise: that the standard of care is based on medical textbooks, which may also be out of date by...Reference1. Sox H and Griner P. An invitation to join a controversy. Ann Intern Med. 1992;116:422-3. LinkGoogle Scholar1. Sox H and Griner P. An invitation to join a controversy. Ann Intern Med. 1992;116:422-3. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: Richard Bettigole, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byStructure of a primary care support system to coordinate comprehensive care for children and families infected/affected by human immunodeficiency virus in a managed care environment 1 August 1992Volume 117, Issue 3Page: 268-268KeywordsInformation storage and retrieval ePublished: 1 December 2008 Issue Published: 1 August 1992 PDF downloadLoading ...
Bioactivation of Mitomycin C by Xanthine Dehydrogenase From EMT6 Mouse Mammary Carcinoma Tumors
Authors: Daniel L. Gustafson, Chris A. Pritsos
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : Mitomycin C is an anti-neoplastic antibiotic requiring bioactivation to an alkylating species or to an intermediate capable of generating oxygen radicals for its toxic effect. The enzymes responsible for the in vivo activation of mitomycin C have been proposed to include NADPH-cytochrome-c reductase, DT-diapho-rase, and xanthine oxidase. Purpose : In this study, xanthine dehydrogenase, an enzyme structurally similar to xanthine oxidase, was assessed for its ability to activate mitomycin C. Partially purified xanthine dehydrogenase, from EMT6 mouse mammary tumors, was investigated for its ability to bioactivate mitomycin C under both aerobic and hypoxic conditions. Methods : We conducted this analysis by measuring mitomycin C-induced oxygen consumption, alkylating potential, and mitomycin C consumption and metabolite formation as determined by high-pressure liquid chromatography analysis. Results : Bioactivation of mitomycin C by xanthine dehydrogenase under both aerobic and hypoxic conditions gave rise to the formation of a metabolite, 2, 7-diaminomitosene. Formation of this metabolite and alkylating ability were greater under hypoxic than under aerobic conditions and were increased when the pH was decreased from 7.4 to 6.0. Mitomycin C consumption was the same under both aerobic and hypoxic conditions and was independent of pH. Oxygen consumption studies showed thatxanthine dehydrogenase-activated mitomycin C consumed oxygen at a much lower rate than xanthine oxidase-activated mitomycin C. Conclusions : Xanthine dehydrogenase activated mitomycin C appears to be a good alkylating species but a relatively poor generator of reactive oxygen when compared with xanthine oxidase activation under aerobic conditions. Implication : Xanthine dehydrogenase may play an important role in the bio-activation of mitomycin C to an alkylating species under both aerobic and hypoxic conditions. [J Natl Cancer Inst 84: 1180–1185, 1992]
Peripheral and Central Ventilatory Responses in Central Sleep Apnea with and without Congestive Heart Failure
Authors: PETER SOLIN, TEANAU ROEBUCK, DAVID P. JOHNS, E. HAYDN WALTERS, MATTHEW T. NAUGHTON
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Given that the apnea–ventilation cycle length during central sleep apnea (CSA) with congestive heart failure (CHF) is ∼ 70 s, we hypothesized that rapidly responsive peripheral CO2 ventilatory responses would be raised in CHF-CSA and would correlate with the severity of CSA. Sleep studies and single breath and rebreathe hypercapnic ventilatory responses (HCVR) were measured as markers of peripheral and central CO2 ventilatory responses, respectively, in 51 subjects: 12 CHF with no apnea (CHF-N), 8 CHF with obstructive sleep apnea (CHF-OSA), 12 CHF-CSA, 11 CSA without CHF ("idiopathic" CSA; ICSA), and 8 normal subjects. Single breath HCVR was equally elevated in CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (0.58 ± 0.09 [mean ± SE] and 0.58 ± 0.07 versus 0.23 ± 0.06, 0.25 ± 0.04, and 0.27 ± 0.02 L/min/Pet CO2 mm Hg, respectively, p < 0.001). Similarly, rebreathe HCVR was elevated in both CHF-CSA and ICSA groups compared with CHF-N, CHF-OSA, and normal groups (5.80 ± 1.12 and 3.53 ± 0.29 versus 2.00 ± 0.25, 1.44 ± 0.16, and 2.14 ± 0.22 L/min/Pet CO2 mm Hg, respectively, p < 0.001). Furthermore, in the entire CHF group, single breath HCVR correlated with central apnea–hypopnea index (AHI) (r = 0.63, p < 0.001) and percentage central/total apneas (r = 0.52, p = 0.022). Rebreathe HCVR correlated with awake PaCO2 (r = − 0.61, p < 0.001), but not with central AHI or percantage central/total apneas independent of its relationship with single breath HCVR. In conclusion, in subjects with CHF, raised central CO2 ventilatory response predisposes to CSA promoting background hypocapnia and exposing the apnea threshold to fluctuations in ventilation, whereas raised and faster-acting peripheral CO2 ventilatory response determines the periodicity and severity of CSA.
DNR Orders and Medical Futility
Authors: Diane Czlonka
Journal: JAMA (1995)

<h3>To the Editor.</h3> —The article by Dr Curtis and colleagues<sup>1</sup>on the use of the medical futility rationale for do-not-attempt-resuscitation (DNAR) orders and the accompanying Editorial by Ms Alpers and Dr Lo<sup>2</sup>offer fewer reasons for concern about the use of futility than they suppose. First of all, the analysis by Curtis and colleagues on the use of quantitative futility is contaminated by the fact that of the 75 patients whose DNAR orders were in part supported by an appeal to quantitative futility, 45 (60%) also involved appeals to qualitative futility, and the great majority were in part determined by patient or family choice as well. Thus, the finding that a third of the patients to whom quantitative futility was applied were given probabilities of survival to discharge of greater than 5% tells us nothing about what likelihood of survival the residents thought would warrant a DNAR order
Zidovudine Use to Reduce Perinatal HIV Type 1 Transmission in an Urban Medical Center
Authors: Andrew A. Wiznia
Journal: JAMA (1996)

To evaluate whether zidovudine treatment was accepted and used by pregnant women subsequent to the release of the results of a multicenter, randomized, placebo-controlled trial (AIDS Clinical Trial Group [ACTG] Protocol 076) that showed that zidovudine significantly reduced maternal-infant human immunodeficiency virus (HIV) type 1 transmission.Prospective study.A community hospital with an integrated, multidisciplinary HIV-dedicated program located in an impoverished, HIV-endemic urban setting.All HIV-infected pregnant women identified after the release of the ACTG 076 results who were offered zidovudine therapy to reduce maternal-infant transmission.Only 49 of the 125 HIV-infected pregnant women delivering at our site during this study period were identified prenatally. Perinatal zidovudine therapy was chosen by 37 (75%) of 49 women. Women refusing zidovudine were more likely to report injection drug use as their HIV risk factor and to continue to use drugs during their pregnancy. Of women choosing zidovudine and delivering, 24 of 36 received all components of their elected therapy. The intrapartum dose was missed by 12 women, 4 of whom also missed their prescribed prenatal oral therapy. Lack of adherence to chosen therapy was associated with continued cocaine use during pregnancy.Zidovudine therapy to interrupt vertical transmission of HIV was not widely used by these HIV-infected pregnant women. Further studies evaluating factors affecting the acceptance and use of recently published public health recommendations are needed.
Prenatal Detection of Neural Tube Defects
Authors: Aubrey Milunsky
Journal: JAMA (1980)

Neural tube defects (NTDs) are among the most common major congenital malformations in the United States. Prenatal detection is possible in about 95% of cases by assaying amniotic fluid for α-fetoprotein (AFP), which leaks from open lesions. In 20,000 pregnancies, 334 (1.7%) had a raised level of AFP. Of these, 136 (40.7%) had open NTDs, 90 (26.9%) had other fetal defects or conditions, and 108 (32.3%) almost invariably had admixed fetal blood. Pregnancy was electively terminated in 11 cases in which the AFP concentration was thought to be elevated but in which the fetus was apparently normal (0.06%), but in only two of these cases was there no explanation for the raised level of AFP. The practical false-positive rate was considerably below 0.06%. Patients at risk for bearing children with NTDs should be counseled and offered prenatal diagnosis. (<i>JAMA</i>1980;244:2731-2735)
Dynamics of acquisition and loss of carriage of Staphylococcus aureus strains in the community: The effect of clonal complex
Authors: Ruth R. Miller, A. Sarah Walker, Heather Godwin, Rowena Fung, Antonina Votintseva, Rory Bowden, David Mant, Timothy E.A. Peto, Derrick W. Crook, Kyle Knox
Journal: Journal of Infection (2014)

Staphylococcus aureus nasal carriage increases infection risk. However, few studies have investigated S. aureus acquisition/loss over >1 year, and fewer still used molecular typing.1123 adults attending five Oxfordshire general practices had nasal swabs taken. 571 were re-swabbed after one month then every two months for median two years. All S. aureus isolates were spa-typed. Risk factors were collected from interviews and medical records.32% carried S. aureus at recruitment (<1% MRSA). Rates of spa-type acquisition were similar in participants S. aureus positive (1.4%/month) and negative (1.8%/month, P = 0.13) at recruitment. Rates were faster in those carrying clonal complex (CC)15 (adjusted (a)P = 0.03) or CC8 (including USA300) (aP = 0.001) at recruitment versus other CCs. 157/274 (57%) participants S. aureus positive at recruitment returning ≥ 12 swabs carried S. aureus consistently, of whom 135 carried the same spa-type. CC22 (including EMRSA-15) was more prevalent in long-term than intermittent spa-type carriers (aP = 0.03). Antibiotics transiently reduced carriage, but no other modifiable risk factors were found.Both transient and longer-term carriage exist; however, the approximately constant rates of S. aureus gain and loss suggest that 'never' or truly 'persistent' carriage are rare. Long-term carriage varies by strain, offering new explanations for the success of certain S. aureus clones.
Reduced suppressor cell activity in congestive cardiomyopathy and in myocarditis.
Authors: R Eckstein, W Mempel, H D Bolte
Journal: Circulation (1982)

We studied suppressor cell function in 10 patients who had congestive cardiomyopathy, 13 patients who had myocarditis and 98 healthy controls. Myocardial biopsy, coronary arteriography and left ventricular angiography were used to define and differentiate congestive cardiomyopathy and myocarditis. The suppressor component of the immune response was assessed by examining the in vitro responses of peripheral blood lymphoid (PBL) cells under standard conditions. Briefly, PBL cells were incubated with concanavalin A to stimulate suppressor activity. Induced activity was measured by the ability of PBL cells to inhibit 3H-thymidine uptake of nonstimulated autologous cells when subsequently presented with allogenic or mitogenic stimuli.
Systematic review of spinal manipulation: Including different techniques
Authors: A. Moore
Journal: Journal of the Royal Society of Medicine (2006)

If the paper by Ernst and Canter (April 2006 JRSM1) was produced in the name of science or to support evidence based practice then the quality of the paper is of serious concern.

The systematic reviews surveyed by Ernst and Canter used various terms for the intervention: `manipulation' and `manual therapy' and `mobilization'. The terms were usually poorly defined even in the original studies. These terms describe quite distinct types of manual intervention, producing differing physiological effects. They cannot be used interchangeably and are not equivalent to spinal manipulation. Moreover, the methodology is intrinsically remote from the primary data, and the data the authors reviewed did not justify the conclusions they drew.

It is unfortunate that Ernst and Canter's cut-off date excluded a recent rigorous systematic review and meta-analysis by Licciardone et al.2 which evaluated the effectiveness of osteopathic manipulative treatment for low back pain. This study concluded that osteopathic manipulative treatment `... significantly reduces low back pain. The level of pain reduction is greater than expected from placebo effects alone and persists for at least three months'.

The professions which utilize manual therapy recognize the need for more evidence to support the range of manual therapy techniques and are already engaged in this process; access to funding remains a considerable barrier to conducting as much research as the professions would like.
Valvular Disease of the Heart
Authors: R. H. Semple
Journal: BMJ (1850)

There is, perhaps, no department of medical science in whichi such rapid and satisfactory progress hais been made of late-years, as in the Diagnosis and Pathology of the Diseases of the Heart.At the com- mencement of the present century, very little amurate knowledge w entertained concerning the morbid conditions of this important organ; and it is painful to reflect upon the serious errors in practice, which must have arisen when cardiac pathology was in a state of obscurity.The great work of Laenec, while it investigated and described with considerable accuracy the diseases of the lungs, and threw a flood of light upon their treatment, failed in gving a similar degree of pre- cision to the physical examination of the central organ of the circulation.When I wa a student in this metropolis, the Diseases of the Heart were in progress of investigation by a number of acute and laborious observers; but, even in the best schools of medicine, the nature of the healthy sounds was stil a matter of doubt, speculation, and discussion; while the morbid sounds, although attentively observed and accurately described, were not attributed, in all cases, to their real causes, or connected with their true pathological conditions.At the present dav it may be said, I think without exaggeration, that the diagnosis of the Diseases of the Heart is now so well under- stood, that it may be almost ranked among the number of the exact scieuces.The labours of our illustrious countryman Dr. Hope, and the no less important researches of Dr. C. J. B.Williams, have left hardly any room for doubting the accurcy of the laws which are now laid down as guides for the physical investigation of the Heart.The healthy sounds have been referred to their true causes by experiments and remonings so satisfactory and conclusive, as to carry conviction to all rational minds; while the morbid sounds have not only been accurately con- nected with their true pathological phenomens, but have been localisedVol" 1x.
Prevention of Acute Allograft Rejection by Antibody Targeting of TIRC7, a Novel T Cell Membrane Protein
Authors: Nalân Utku, Thomas Heinemann, Stefan G Tullius, Grit-Carsta Bulwin, Sören Beinke, Richard S Blumberg, Francisca Beato, Jeffrey Randall, Ryoji Kojima, Liliana Busconi, Erle S Robertson, Ralf Schülein, Hans-Dieter Volk, Edgar L Milford, Steven R Gullans
Journal: Immunity (1998)
Back from Basra
Authors: James Owen Drife
Journal: BMJ (2007)

When your son joins the Territorial Army it seems no big deal at first. Weekends on Salisbury Plain are healthy exercise for a lawyer. From time to time he helps to fire off a royal salute or invites you to a rather jolly mess dinner.

Then reality bites. Volunteers are wanted for a tour of duty “somewhere overseas.” Not you, son, surely? Tell them you're an essential worker. Oh. OK. I suppose it's a matter of …
Infantile cardiomyopathy with histiocytoid change in cardiac muscle cells. Report of six patients.
Authors: V J Ferrans, H A McAllister, W H Haese
Journal: Circulation (1976)

Clinical and pathologic findings are presented in 14 patients (six newly reported, eight described previously), all children ranging in age from 6 to 24 months, with a clinicopathologic syndrome termed "infantile cardiomyopathy with histiocytoid change in cardiac muscle cells." This syndrome is manifested clinically by severe, eventually fatal cardiac arrhythmias, and is characterized pathologically by cardiac hypertrophy and by a distinctive type of focal degeneration of the muscle cells, which lose their myofibrils, undergo marked mitochondrial hyperplasia, become rounded in shape and enlarged, and resemble histiocytes. Evidence is presented to support the conclusions that these manifestations are those of a cardiomyopathy, that cardiac hypertrophy precedes the onset of the clinical features, that the focal degeneration is likely to be a cause rather than a consequence of the arrhythmias, and that the latter develop only in the late stages of the disorder. The etiology of this cardiomyopathy remains unclear.
Primary Adrenocortical Nodular Dysplasia Presented as Adrenal Adenoma by Functional Scintigraphy
Authors: R V G GARC??A-MAYOR, L P??REZ MENDEZ, C P??RAMO, A ANDRADE, R GUITIAN, M BUTRON
Journal: Clinical Nuclear Medicine (1993)

GARCIA-MAYOR, R. V. G.*; MENDEZ, L. PÉREZ*; PÉRAMO, C.*; ANDRADE, A.†; GUITIAN, R.‡; BUTRON, M.§ Author Information
Values, Health Care Reform, and Universal Participation
Authors: Mary Crowley
Journal: New England Journal of Medicine (2009)

In his Perspective article in the July 30, 2009, issue of the Journal, 1 Brett was critical of an overreliance on one American value — choice — and argued that equity was at least as important. We at the Hastings Center (a nonpartisan bioethics research institute) believe that a sophisticated and nuanced account of values can and should be the beating heart of health care reform. To date, however, the nuts and bolts of reform have been front and center, while the underlying values have received scant attention or, worse, been used as cudgels to batter opponents. We need to engage . . .
TYPHUS FEVER IN A PREVIOUSLY VACCINATED LABORATORY WORKER
Authors: Herman Gold
Journal: JAMA (1942)

History of Present Illness.—  Dr. B. H., a white woman aged 45, was well until Feb. 7, 1942, when malaise, slight headache and fever developed. At 7 p. m. her temperature was 99 F. The next day the symptoms were unchanged and she reported to work on the 9th; she felt well during the morning but in the afternoon she was unduly fatigued and feverish. There was loss of appetite and considerable sweating. On the 11th severe aching pain developed across the back of the head and lasted throughout the duration of fever. There was no vomiting and the bowel movements were regular. Fever and headache were the outstanding complaints when one of us (H. G.) saw the patient on the 12th at 9 p. m. Her temperature then was 102.4 F., with a corresponding rise in the pulse and respiration. The skin was dry and hot. The tongue