tbuckley/cabot-search huggingface dataset:
Calcium ion concentrations and DNA fragmentation in target cell destruction by murine cloned cytotoxic T lymphocytes.
Authors: N L Allbritton, C R Verret, R C Wolley, H N Eisen
Journal: The Journal of Experimental Medicine (1988)

To investigate the destruction of target cells by murine CTLs, we examined intracellular Ca2+ concentrations ([Ca2+]i) and DNA fragmentation in target cells. Changes in [Ca2+]i were followed by flow cytometry by loading the cells with indo-1, a Ca2+-binding fluorescent dye, and determining the ration of fluorescence intensities at 405 nm (emission maximum for Ca2+-bound dye) over 480 nm (emission maximum for the free dye). Within minutes after interacting with the cytolytic granule fraction that had been isolated from CTLs, [Ca2+]i in target cells was strikingly increased. A pronounced increase in [Ca2+]i was also observed in target cells when they were specifically recognized by intact CTLs. Since ionomycin, a Ca2+ ionophore, caused a similar increase in [Ca2+]i and lysed cells (provided that extracellular Ca2+ was present), it appears that a sustained high level of [Ca2+]i is cytolytic. In contrast with other cells, CTLs, which have been shown to be refractory to granule-mediated lysis and to be poor targets for other CTLs, did not manifest an elevation in [Ca2+]i when they were similarly loaded with indo-1 and treated with isolated granules. The characteristic cleavage of target cell DNA into nucleosome-sized fragments was also induced by isolated granules as well as by valinomycin, a K+ ionophore, but not by ionomycin. The results support the view that lysis of most target cells by cloned CTLs is due primarily to target cell membrane changes that are fundamentally equivalent to the formation of nonspecific ion channels. The resulting large increase in [Ca2+]i is probably responsible for target cell lysis; and changes in intracellular ion concentrations also appear to be responsible for DNA fragmentation, probably by activating endogenous target cell endonucleases.
Visit-to-Visit Blood Pressure Variability Is a Novel Risk Factor for the Development and Progression of Diabetic Nephropathy in Patients With Type 2 Diabetes
Authors: Hiroshi Okada, Michiaki Fukui, Muhei Tanaka, Shinobu Matsumoto, Yusuke Mineoka, Naoko Nakanishi, Mai Asano, Masahiro Yamazaki, Goji Hasegawa, Naoto Nakamura
Journal: Diabetes Care (2013)

OBJECTIVE Recent study has suggested that not only the presence of hypertension but also the variability in systolic blood pressure (SBP) are risk factors for vascular disease and organ damage. The aim of this study was to investigate the relationship between visit-to-visit variability in SBP and change in urinary albumin excretion (UAE) or development of albuminuria in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We measured SBP in 354 consecutive patients at every visit during 1 year and calculated the coefficient of variation (CV) of SBP. We performed a follow-up study to assess change in UAE or development of albuminuria, the mean interval of which was 3.76 ± 0.71 years. Then, we evaluated relationships of variability of SBP to diabetic nephropathy using multiple regression analysis and multiple Cox regression model. RESULTS Multiple regression analysis demonstrated that CV of SBP was independently associated with change in UAE (β = 0.1758; P = 0.0108). Adjusted Cox regression analyses demonstrated that CV of SBP was associated with an increased hazard of development of albuminuria; hazard ratio was 1.143 (95% CI 1.008–1.302). CONCLUSIONS Visit-to-visit variability in SBP could be a novel risk factor for the development and progression of diabetic nephropathy in patients with type 2 diabetes.
Recurrent Cardiac Events in Survivors of Ventricular Fibrillation or Tachycardia
Authors: Greg C. Larsen
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine when survivors of ventricular tachycardia (VT) or ventricular fibrillation (VF) might most safely return to driving. <h3>Design.</h3> —Consecutive case series of 501 VT and VF survivors discharged alive between August 1978 and October 1989 and followed from 0 to 117 months (mean, 26 months). <h3>Setting.</h3> —Cardiac arrhythmia service of a university hospital. <h3>Patients.</h3> —The study group comprised 290 consecutive patients with sustained VT and 211 patients with VF who underwent electrophysiological studies and were discharged alive (78% male; mean age, 59 years). The mean ejection fraction (available in 338 patients) was 0.42. <h3>Interventions.</h3> —Antiarrhythmic drug testing for all patients was guided by serial electrophysiological testing. Overall, 227 patients (45%) were discharged on conventional antiarrhythmic agents, 115 (23%) on amiodarone, 39 (8%) received an implantable defibrillator, and 120 (24%) received no specific antiarrhythmic therapy. <h3>Main Outcome Measures.</h3> —Main outcomes included any event that could hamper a patient's ability to operate a motor vehicle. Specifically, these events included recurrent VF, poorly tolerated, hemodynamically unstable VT, syncope, sudden cardiac death, and implantable defibrillator discharge. <h3>Results.</h3> —Event risks were assessed during the first year after hospital discharge because that is when most patients decide whether to begin driving again. The 1-year outcome event rate for all 501 patients was 17%. Three distinct periods of risk were identified. The monthly hazard rate was highest in the first month after hospital discharge (4.22% per month), intermediate in months 2 through 7 (1.81% per month), and lowest in months 8 through 12 (0.63% per month). The 191 patients for whom no successful conventional antiarrhythmic drug could be found during electrophysiological testing experienced a persistently high monthly event risk (1.6%) during months 8 through 12. <h3>Conclusions.</h3> —All survivors of VT or VF should refrain from driving during the first month after hospital discharge when the hazard for events that could impair their ability to drive is greatest. Our data would support restricting driving for most patients until the eighth month after hospital discharge, when risk becomes lowest. Restriction might be lengthened in patients for whom electrophysiological testing finds no satisfactory conventional antiarrhythmic agent because their risk remains higher than average even after 7 months. Individualized recommendations should be allowed because the accident rate for patients who actually suffer sudden death is low. (<i>JAMA</i>. 1994;271:1335-1339)
Abstract 3019: Demethylation of RB regulator MYPT1 by histone demethylase LSD1 promotes cell cycle progression in cancer cells
Authors: Hyun-Soo Cho, Yusuke Nakamura, Ryuji Hamamoto
Journal: Cancer Research (2011)

Abstract Histone demethylase LSD1 (also known as KDM1 and AOF2) is active in various cancer cells, but its biological significance in human carcinogenesis is unexplored. In this study, we explored hypothesized interactions between LSD1 and MYPT1, a known regulator of RB1 phosphorylation. We found that MYPT1 was methylated in vitro and in vivo by histone lysine methyltransferase SETD7 and demethylated by LSD1, identifying Lys 442 of MYPT1 as a target for methylation/demethylation by these enzymes. LSD1 silencing increased MYPT1 protein levels, decreasing the steady-state level of phosphorylated RB1 (Ser 807/811) and reducing E2F activity. MYPT1 methylation status influenced the affinity of MYPT1 for the ubiquitin-proteasome pathway of protein turnover. MYPT1 was unstable in murine cells deficient in SETD7, supporting the concept that MYPT1 protein stability is physiologically regulated by methylation status. LSD1 overexpression could activate RB1 phosphorylation by inducing a destabilization of MYPT1 protein. Taken together, our results comprise a novel cell cycle regulatory mechanism mediated by methylation/demethylation dynamics, and they reveal the significance of LSD1 overexpression in human 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 3019. doi:10.1158/1538-7445.AM2011-3019
Efficacy of anti-intercellular adhesion molecule-1 immunotherapy on immune responses to allogeneic hepatocytes in mice
Authors: Ginny L. Bumgardner, Jiashun Li, Marie Heininger, Charles G. Orosz
Journal: Hepatology (1998)

Adhesion molecules appear to play important roles in vascularized organ allograft rejection, because antibodies directed against them are effective in prolonging survival of vascularized organ allografts in rodents. However, the efficacy of these agents for cellular allografts is unknown. The current studies were undertaken to determine the role of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on host immune responses to purified hepatocytes. Host mice (C3H, H-2(k)) grafted with hepatocytes in sponge matrix allografts (HC-SMA) received IgG isotype control, anti-ICAM-1, or anti-VCAM-1 monoclonal antibody (mAb) on days 0 through 9 after grafting. Twelve to 14 days later, host cells infiltrating the HC-SMA were assessed for the development of allospecific cytolytic T cells (allo-CTLs). Treatment with anti-ICAM-1 or anti-VCAM-1 mAb resulted in significantly decreased recruitment of host cells into HC-SMA (P < .035). However, only anti-ICAM-1 mAb resulted in abrogation of development of allo-CTLs in HC-SMA (P = .001). C3H (H-2(k)) hosts grafted with allogeneic hepatocytes from control C57BL/6 (H-2(b)) or ICAM-1 knockout [H-2(b)] mice elicited the development of allo-CTLs in HC-SMA (P = not significant). Furthermore, there was no difference in the development of allo-CTLs in HC-SMA of control hosts [C57BL/6, H-2(b)] compared with ICAM-1 knockout hosts (H-2(b)) (P = not significant). Treatment with anti-ICAM-1 mAb had no effect on the development of allo-CTLs in ICAM-1 knockout (H-2(b)) hosts bearing HC-SMA. The immunosuppressive effect of host treatment with anti-ICAM-1 mAb does not appear to be a consequence of simple blockage of donor hepatocyte or host immune cell expression of ICAM-1, but suggests a potential inhibitory effect on host immune cell activation or function, as well as an effect on recruitment of host cells to the allograft.
Treatment of Zoster with Idoxuridine in Dimethyl Sulphoxide. Results of Two Double-blind Controlled Trials
Authors: B. E. Juel-Jensen, F. O. MacCallum, A. M. R. Mackenzie, M. C. Pike
Journal: BMJ (1970)

The antiviral effect of 5% idoxuridine in dimethyl sulphoxide intermittently applied and of 40% idoxuridine in dimethyl sulphoxide continuously applied for four days to the lesions in patients with zoster of recent onset was studied in two double-blind controlled trials. Most, but not all, of the patients receiving intermittent active treatment had pain for a short period only. The effect of continuous treatment was striking: pain had disappeared within nine days in all the patients and healing was accelerated. The results were statistically significant.
Systemic Effects of Nitrofurazone-Impregnated Urinary Catheters in Trauma Patients
Authors: Jakob Stensballe
Journal: Annals of Internal Medicine (2008)

Letters18 March 2008Systemic Effects of Nitrofurazone-Impregnated Urinary Catheters in Trauma PatientsJakob Stensballe, PhDJakob Stensballe, PhDFrom Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-148-6-200803180-00025 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Stinnette for his interest. We found no evidence of adverse side effects, such as anemia and liver or respiratory failure, related to the nitrofurazone impregnation of the silicone catheter. This is in accordance with Marion-Landais and colleagues' (1) finding that nitrofurazone is not absorbed to the surrounding tissue or systemically. Furthermore, the observed adverse events in the study were found to be unrelated to the nitrofurazone impregnation and were more likely related to catheterization.Jakob Stensballe, PhDCopenhagen University HospitalDK-2100 Copenhagen, DenmarkReference1. Marion-Landais G, Heotis JP, Mertz JL, Diaz JR, Van Hart DC, Newsom JH, et al. Non-absorption of nitrofurazone from the urethra in men. Curr Ther Res Clin Exp. 1976;19:550-3. [PMID: 820520] MedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Copenhagen University Hospital, DK-2100 Copenhagen, Denmark.Disclosures: Dr. Stensballe is the recipient of an unrestricted research grant from Coloplast A/S. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoInfection Risk with Nitrofurazone-Impregnated Urinary Catheters in Trauma Patients Jakob Stensballe , Michael Tvede , Dagnia Looms , Freddy Knudsen Lippert , Benny Dahl , Else Tønnesen , and Lars Simon Rasmussen Systemic Effects of Nitrofurazone-Impregnated Urinary Catheters in Trauma Patients William A. Stinnette Metrics Cited byAntimicrobial Coatings and Other Surface Modifications for Infection PreventionHeart Failure with Sunitinib; Prolonged QT Interval, Syncope, and Delirium with Galantamine; Memantine-Induced Hepatitis; Cabergoline-Associated Erythema Nodosum; “Sleep Driving” and the Use of Nonbenzodiazepine Hypnotics; Atypical Fractures in Postmenopausal Women Taking Alendronate; Drug-Related Problems in Patients with Human Immunodeficiency Virus 18 March 2008Volume 148, Issue 6Page: 486KeywordsAdverse eventsAnemiaCatheterizationConflicts of interestLiverResearch grantsRespiratory failure ePublished: 18 March 2008 Issue Published: 18 March 2008 Copyright & PermissionsCopyright © 2008 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
THE IN VITRO DESENSITIZATION OF SENSITIVE CELLS BY TRYPSIN
Authors: John R. David, H. S. Lawrence, L. Thomas
Journal: The Journal of Experimental Medicine (1964)

Peritoneal exudate cells from animals exhibiting delayed hypersensitivity are inhibited from migrating in vitro by specific antigen. This inhibition is completely abolished by pretreatment of the sensitive cells with trypsin. The action of trypsin is prevented by soybean trypsin inhibitor. The results of experiments with mixtures of normal and sensitive cells suggest that trypsin alters an immunologic capacity of the sensitive cells. Trypsinized sensitive cells are capable of passively transferring delayed hypersensitivity and peritoneal cells taken from recipient animals are inhibited from migrating in vitro by specific antigen. These results suggest that the cells rapidly resynthesize the material removed by trypsin. The possible nature of the material removed by trypsin is discussed.
The Work Week of Physicians in Private Practice
Authors: Howard A. Rusk, Harold S. Diehl, Robert W. Barclay, Paul K. Kaetzel
Journal: New England Journal of Medicine (1953)

RECOGNITION that the health of the people is fundamental to the full achievement of national potentials, that the key role in health is played by the physician and that the volume of services rendered by physicians must be sufficient to meet these responsibilities has prompted a variety of professional organizations, governmental agencies and other interested groups to develop considerable data concerning the sociologic and economic aspects of the medical profession. The American Medical Association, for example, has reported on the size of the physician population, its composition by age groups, its make-up by field of specialization and type of practice . . .
Roentgenology of the Spleen and Pancreas
Authors: Antonio Rodriguez-Antunez
Journal: JAMA (1968)

<i>Roentgenology of the Spleen and Pancreas</i>provides a concise and orderly survey of the disease processes involving the spleen and pancreas. The embryological, anatomical, and physiological aspects of these organs are briefly considered. These factors aid in the understanding of the findings later described. Methods of examination by roentgen rays are discussed, starting with plain film diagnosis, then going to conventional studies utilizing contrast media, and finally presenting the various special procedures which are utilized. The author provides useful hints for interpreting the various studies and a brief description of the technique for the special procedures. He presents adequate description of the normal findings and the normal variants, as well as the advantages and limitations of each modality of examination. The disease processes are clearly described, and descriptions in the text are well illustrated by a large number of good reproductions. This book will have value primarily in the formal
COLICINE K
Authors: Walther F. Goebel, Guy T. Barry, Theodore Shedlovsky
Journal: The Journal of Experimental Medicine (1956)

An apparatus for maintaining the pH of an actively growing bacterial culture at constant level has been described. Using this apparatus it has been shown that the production of maximal amounts of colicine K from a strain of E. coli known as K235 is dependent upon an enriched nutrient medium which is maintained at pH 7.0.
THE OCCURRENCE OF DIABETES DURING PREGNANCY IN A WOMAN BEARING LARGE BABIES
Authors: Harold Bowcock
Journal: JAMA (1930)

The interesting observation that the babies of diabetic mothers are often oversize has been recorded occasionally in medical literature. Of six babies born of diabetic mothers, at term, Bowen<sup>1</sup>reports that their weights were 6, 7 and 10 pounds; 9 pounds 2 ounces; 10 pounds 6 ounces, and 10 pounds 10 ounces. Springer<sup>2</sup>quotes the finding of Colorni that 19.5 per cent of the fetuses of diabetic mothers are oversize. Joslin<sup>3</sup>records the opinion of Blanco that a fat baby born dead suggests the examination of the parents for diabetes, and states that these observations correspond to the overgrowth that he has noted in children previous to the onset of diabetes.<sup>4</sup> The appearance of true diabetes with typical symptoms and hyperglycemia is a more frequent occurrence during pregnancy than the occurrence of pregnancy in a diabetic individual.<sup>5</sup>Strouse and Daly<sup>6</sup>suggest that some women
English surgeons may at last be about to become doctors
Authors: Roger Dobson
Journal: BMJ (2005)

After a century and a half of being called Mr, change is in the air, with the president of the Royal College of Surgeons, Hugh Phillips, hinting that the days of Mr and Miss as titles for surgeons may be numbered.

Writing about the public consultation over plans for the introduction of non-medically qualified surgical care practitioners, Mr Phillips says it is important that patients know who's who.

“The issue of job title is part of the public consultation, and this is not easy resolvable,” he says in the Annals of the Royal College of Surgeons of England (2005:87(suppl): 153; doi: 10.1308/147363505X45584).

He told the BMJ : “There has been concern recently about who people are in the health service—who is actually treating …
Relation between alcohol and nose bleeds
Authors: G W McGarry, S Gatehouse, J Hinnie
Journal: BMJ (1994)

Nose bleeds in adults are the commonest reason for emergency admission to an otolaryngology ward, but the cause of the condition remains unknown. Case reports and clinical experience suggest an association between nose bleeds and regular, high alcohol consumption.1

The possibility that alcohol is a causal factor in nose bleeds is supported by evidence of profound cardiovascular and haemostatic effects producted by even moderate alcohol consumption. We conducted a prospective case- control study to compare the alcohol habits of adults with nose bleeds with those of controls being treated for other otorhinolaryngological conditions.

The alcohol habits of 140 consecutive patients admitted with nose bleeds (79 men; mean age 54.5 years, range 23-93) were compared with those of 113 age and sex matched controls selected from patients being treated for otorhinolaryngological conditions other …
MODERN TREND IN CHILDREN'S CLOTHING
Authors: Mark Silverberg
Journal: JAMA (1927)

<h3>To the Editor:</h3> —For more than thirty-eight years we have been manufacturing children's garments, from first long clothes to dresses for girls of 12 years. During the past year, for the first time in our experience, we received complaints that the neck measures of our dresses for babies 1, 2 and 3 years of age were not large enough. So persistent have these complaints become that we recently adopted patterns whereby the necks will be made 1 inch larger on these sizes than heretofore. We thought the matter interesting enough to bring to your notice. Can it be possible that still another effect of prohibition has been unearthed? And, by the way, an interesting phenomenon is the very large number of complaints from California. Another manifestation of the glorious climate? If anybody remains unsatisfied with the progress made in these United States, consider the evolution or, rather, the diminution of
The rise of regulation in the NHS
Authors: K. Walshe
Journal: BMJ (2002)

The current British government has created five national agencies to regulate the NHS. These new arrivals are simply additions to an already crowded regulatory landscape. But, if politicians can be persuaded to let go, the new regulators of the NHS could provide a genuinely new approach to improving performance and management

During the past four years the British government has created five new national agencies to regulate the NHS in England (box).1 2 3 4 The government has moved away from using markets, competition, and contracting to manage performance in the NHS. But it has been unwilling to rely on traditional bureaucratic structures to exert control, and has turned increasingly to regulation.

In this article, I describe how and why organisational regulation in the NHS in England has grown in recent years. I examine how regulation was used in the NHS in the past and describe the characteristics of the new regulatory agencies. Finally, I use information from the wider literature on regulation to examine the regulatory model adopted by these new agencies and to explore what they might learn from regulation in other settings.

#### Summary points

Over the past 20 years, regulation has increased in Britain's private and public sectors

In the past four years the British government has created five new national agencies to regulate the NHS

The new agencies could be the start of a new approach to improving performance and management in the NHS

The new agencies could learn from regulators in other sectors and adopt a responsive approach to regulation

#### New national agencies to regulate the NHS

National Institute for Clinical Excellence

Commission for Health Improvement

Modernisation Agency

National Patient Safety Agency

National Clinical Assessment Authority

Regulation is “sustained and focused control exercised by a public agency over activities which are valued by a community.”5 The key features of regulation are that …