tbuckley/cabot-search huggingface dataset:
Abstract C31: NAMPT inhibition combined with radiation enhances cell death in a prostate cancer model
Authors: Shuraila Zerp, Baukelien Van Triest, Ben Floot, Conchita Vens, Marcel Verheij
Journal: Cancer Research (2012)

Abstract Background and purpose: Prostate cancer patients with localized disease can be treated with radiotherapy. In the present study we investigated the complementary effect of NAMPT inhibitor APO866, on the combination with radiation treatment with respect to prostate tumor cell death. APO866 is a highly specific non-competitive inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme in the regulation of NAD+ biosynthesis. Inhibition of NAMPT could deplete cellular NAD+. According to literature NAMPT may have a prominent role in prostate cancer development and progression. Interestingly for research purposes, prostate cancer cell lines PC3 and LNCaP solely depend on the NAMPT synthesis route for their NAD recovery. Treatment of prostate cancer cells with a combination of ionizing radiation and APO866 shows an enhancement of cell death in vitro as well as in vivo. Results: APO866, in nanomolar concentrations, induces a time- and dose-dependent depletion of cellular NAD+ levels in a panel of human tumor cell lines (U937, J16, LNCaP, PC3 and A431). In vitro, under APO866-mediated reduced NAD+ conditions, solid tumor cell lines PC3 and LNCaP show besides a cytotoxic effect also a decrease in clonogenic survival in combination with ionizing radiation (Dose enhancement factor at 10% survival: 1.34 and 1.45 resp.), which was not caused by radiation-induced enhancement of dsDNA breaks as determined by γ-H2AX nuclear foci formation, nor by induction of apoptosis. In vivo experiments with PC3 xenografts, treated with the APO866/radiation combination, show the combination is more effective than APO866 or radiation treatment alone. The time to reach 300% of the initial tumor volume was in the control group 9.5 days, for APO866 treatment 28.6 days, radiation treatment 51.4 days and for the combined APO866/radiation treatment 76.6 days. Only the combination treatment caused complete initial growth regression. No significant toxicity was observed after any of these treatments. Tumors from animals treated with APO866 showed significant reduced NAD+ levels. Conclusion: NAMPT inhibition through APO866 treatment enhances cell death in combination with radiation in a prostate cancer model. Targeting NAD+ biosynthesis is a promising strategy in combined modality therapy with radiation. Citation Format: Shuraila Zerp, Baukelien Van Triest, Ben Floot, Conchita Vens, Marcel Verheij. NAMPT inhibition combined with radiation enhances cell death in a prostate cancer model [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr C31.
Greater ozone-induced inflammatory responses in subjects with asthma.
Authors: C Scannell, L Chen, R M Aris, I Tager, D Christian, R Ferrando, B Welch, T Kelly, J R Balmes
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

In order to test the hypothesis that ozone (O3)-induced changes in lung function and respiratory tract injury/inflammation are greater in subjects with asthma than in normal subjects, we exposed 18 asthmatic subjects, on separate days, to O3 (0.2 ppm) and filtered air for 4 h during exercise. Symptom questionnaires were administered before and after exposure, and pulmonary function tests (FEV1, FVC, and specific airway resistance [SRaw]) were performed before, during, and immediately after each exposure. Fiberoptic bronchoscopy, with proximal airway lavage (PAL) of the isolated left main bronchus and bronchoalveolar lavage (BAL; bronchial fraction, the first 10 ml of fluid recovered) of the right middle lobe, was performed 18 h after each exposure. The PAL, bronchial fraction, and BAL fluids were analyzed for the following endpoints: total and differential cell counts; total protein, lactate dehydrogenase (LDH), fibronectin, interleukin-8 (IL-8), granulocyte-macrophage colony-stimulating factor (GM-CSF), myeloperoxidase (MPO), and transforming growth factor-beta (TGF beta 2) concentrations. We found a significant O3 effect on FEV1, FVC, SRaw (p < 0.04) and lower respiratory symptoms (p < 0.001) for the asthmatic subjects. Ozone exposure also significantly increased the percent neutrophils in PAL (p < 0.01); percent neutrophils, total protein, and IL-8 in the bronchial fraction (p < 0.001, p < 0.05, and p < 0.01, respectively); and the percent neutrophils, total protein, LDH, fibronectin, IL-8, GM-CSF, and MPO in BAL (p < 0.001, p < 0.01, p < 0.01, p < 0.001, p < 0.05, p < 0.01, and p < 0.001, respectively) for the asthmatic subjects. There were no significant differences in the lung function responses of the asthmatic subjects in comparison with a group of normal subjects (n = 81) previously studied using an identical protocol, although there was a trend toward a greater O3-induced increase in SRaw in the asthmatic subjects (p < 0.13). In contrast, the asthmatic subjects showed significantly greater (p < 0.05) O3-induced increases in several inflammatory endpoints (percent neutrophils and total protein concentration) in BAL as compared with normal subjects who underwent bronchoscopy (n = 20). Our results indicate that asthmatic persons may be at risk of developing more severe O3-induced respiratory tract injury/inflammation than normal persons, and may help explain the increased asthma morbidity associated with O3 pollution episodes observed in epidemiologic studies.
Experimental vaccine may have saved Hamburg scientist from Ebola fever
Authors: A. Tuffs
Journal: BMJ (2009)

A scientist from the Bernard Nocht Institute for Tropical Medicine in Hamburg who was quarantined for a week because of a possible infection with the Ebola fever virus has left the isolation ward of Hamburg University Hospital. She has been transferred to a normal ward, because she had no clinical signs of infection, and neither the virus nor any antibodies against the virus were found in her blood.

This positive development may be due to the use of an experimental vaccine given to the scientist that has never previously been used in humans. The vaccine virus was …
Leukocyte adhesion deficiency‐I variant syndrome (LAD‐Iv, LAD‐III): Molecular characterization of the defect in an index family
Authors: Estelle S. Harris, Tammy L. Smith, Gregory M. Springett, Andrew S. Weyrich, Guy A. Zimmerman
Journal: American Journal of Hematology (2011)

Leukocyte adhesion deficiencies are rare clinical syndromes of impaired host defense that provide novel insights into regulation of immune and inflammatory responses. Leukocyte adhesion deficiency (LAD)-I variant (LAD-Iv), also called LAD-III, is a unique disorder in which inside-out signaling of β₁, β₂, and β₃ integrins on leukocytes and platelets is disrupted, leading to impaired cellular adhesion, recurrent infections, and bleeding. We originally reported the second patient with this disorder to be identified and characterized the adhesive deficiencies and functional phenotype of this subject's leukocytes. Here, we show that the molecular defect in this index subject is a new mutation in FERMT3 (KINDLIN-3) which encodes KINDLIN-3, a cytoskeletal protein that interacts with the cytoplasmic tails of β₁, β₂, and β₃ integrins and is required for inside-out and outside-in signaling of these heterodimers. We also report clinical features and previously unrecognized defects in cells from a new patient, a sibling of the original subject that we described who carries the same FERMT3 mutation. Mutations in FERMT3 have now been shown to be the basis for LAD-Iv/LAD-III in each of the four original patients or families that established this syndrome, including the family that we describe.
Imaging of Giant Cell Arteritis
Authors: FREDERIC DE WINTER, MIRKO PETROVIC, CHRISTOPHE VAN DE WIELE, DIRK VOGELAERS, MARCEL AFSCHRIFT, RUDI ANDRE DIERCKX
Journal: Clinical Nuclear Medicine (2000)

A 63-year-old man with fever of unknown origin was referred for F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). Intensive clinical workup, including computed tomography of the brain, thorax, and abdomen and leukocyte scintigraphy revealed no abnormalities. F-18 FDG PET showed increased FDG uptake in the major thoracic vessels and abnormal splenic FDG accumulation. Temporal artery biopsy confirmed the diagnosis of giant cell arteritis. A follow-up FDG PET scan after 6 weeks of prednisolone treatment showed a marked reduction of the vasculatory and splenic uptake. This case report suggests splenic involvement in giant cell arteritis.
Postmenopausal Hormone Therapy
Authors: Knight Steel
Journal: Annals of Internal Medicine (1993)

Letters15 August 1993Postmenopausal Hormone TherapyKnight SteelKnight SteelSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-119-4-199308150-00029 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The superb review of hormone therapy in postmenopausal women [1] and the associated guidelines [2] did not address the following issues:The possible increase in the risk for developing breast cancer associated with the use of estrogen plus progestin therapy (the most widely used hormone therapy) is the major deterrent to its use. Many studies of estrogen therapy show a small increase in risk among those using it for the longest duration; the data about estrogen plus progestin therapy appear inconclusive. Given the suggestion that any increased risk occurs only after long-term use, why not use the ...References1. Grady D, Rubin SM, Petitti DB, Fox CS, Black D, Ettinger B, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. 1992; 117:1016-37. Google Scholar2. American College of Physicians. Guidelines for counseling postmenopausal women about preventive hormone therapy. Ann Intern Med. 1992; 117:1038-41. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 August 1993Volume 119, Issue 4Page: 347-348KeywordsBreast cancerEstrogen replacement therapyEstrogensGlobal healthHormonal therapyHormones Issue Published: 15 August 1993 Copyright & PermissionsCopyright © 1993 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Prospective Study of Relative Weight, Height, and Risk of Breast Cancer
Authors: Stephanie J. London
Journal: JAMA (1989)

We examined relative weight and height in relation to subsequent breast cancer risk among 115,534 women 30 to 55 years of age and free from cancer in 1976. By 1984, six hundred fifty-eight premenopausal and 420 postmenopausal breast cancers were documented during 734,716 person-years. Among premenopausal women, risk of breast cancer decreased significantly with increasing relative weight (relative risk for the highest category was 0.6). A similar inverse association was seen for recalled relative weight at 18 years of age. Postmenopausal breast cancer was not associated with relative weight, either recent or at age 18. Height was not associated with breast cancer risk among premenopausal women and only weakly related among postmenopausal women. These data suggest that obesity among premenopausal and early postmenopausal women does not increase breast cancer risk substantially.
Bleeding oesophageal varices and hepatic dysfunction in adult polycystic kidney disease.
Authors: P J Ratcliffe, S Reeders, J M Theaker
Journal: BMJ (1984)

A patient with adult polycystic liver and kidney disease presented with haematemesis and melaena and was found to have raised serum creatinine, aspartate transaminase, and alkaline phosphatase values; hypoalbuminaemia; and a prolonged prothrombin ratio. She also had oesophageal varices. With haemodialysis her aspartate transaminase activity fell to normal but she remained hypoalbuminaemic with a prolonged prothrombin ratio. She died after three weeks. Although hepatic cysts do occur in adult polycystic kidney disease, they have been thought not to cause major liver disease. The hepatic cysts in this patient, however, did appear to be associated with portal hypertension and impaired hepatocellular function.
Erythropoietin Treatment of Postural Hypotension in Anemic Type 1 Diabetic Patients With Autonomic Neuropathy
Authors: Andrea S. Winkler, Sabine Landau, Peter J. Watkins
Journal: Diabetes Care (2001)

Postural hypotension (PH) is a feature of autonomic failure that may result from various causes and can be very difficult to treat. Recently, we and others (1, 2, 3) have shown that some patients with severe symptomatic autonomic neuropathy from type 1 diabetes (type 1 DAN) have a normocytic anemia associated with erythropoietin (EPO) deficiency. The treatment of these patients with EPO rapidly corrects their anemia (1) and improves their overall well-being. Preliminary observations by Hoeldtke et al. (3) of the effect of a maximum of 9 weeks of EPO treatment on blood pressure (BP) demonstrated a positive response in four cases of PH in type 1 DAN patients, but evaluation of BP was limited to only two to three readings before and after EPO treatment. These results stimulated the present study, in which we investigated the effect of EPO treatment for 3 months on supine and standing BP in four anemic EPO-deficient type 1 DAN patients.

The patients were treated with recombinant human EPO (25 IU/kg s.c. thrice weekly). All four patients were women (48, 41, 30, and 30 years of age with a duration of diabetes of 13, 24, 19, and 11 years, respectively) and each had normocytic anemia with inappropriately low serum EPO levels. The known causes of anemia were excluded. All of the patients included in the study had pronounced symptomatic PH and at least one other symptom of autonomic neuropathy. …
TCT-647 Predictors of Stent Thrombosis up to 12 Years Follow-up After Drug-Eluting Stent Implantation in Daily Clinical Practice
Authors: RICARDO A. COSTA, Amanda Sousa, Adriana Moreira, Jose d Costa, Galo Maldonado, Manuel N. Cano, cantidio campos neto, Lucas P. Damiani, J Eduardo Sousa
Journal: Journal of the American College of Cardiology (2014)
Do Patients Want to Participate in Medical Decision Making?
Authors: William M. Strull
Journal: JAMA (1984)

Although shared decision making by patients and clinicians has been advocated, little is known about the degree of participation in decision making that patients actually prefer or about clinicians' appreciation of these preferences. We administered questionnaires about three aspects of decision making to 210 hypertensive outpatients and to their 50 clinicians, who represented three types of medical practices. We found that 41% of patients preferred more information about hypertension; clinicians underestimated patient preferences for discussion about therapy in 29% of cases and overestimated 11% (k = .22); and 53% of patients preferred to participate in making decisions, while clinicians believed that their patients desired to participate in 78% of cases. Many patients who preferred not to make initial therapeutic decisions did want to participate in ongoing evaluation of therapy. Thus, clinicians underestimate patients' desire for information and discussion but overestimate patients' desire to make decisions. Awareness of this discrepancy may facilitate communication and decision making.A survey of hypertensive outpatients and their physicians in three different clinic settings revealed differences between patients and physicians in their perceptions of disclosure and decision making. Patients wanted more discussion of therapy and of decisions about treatment but preferred to leave decision making to their clinicians. Physicians underestimated both the amount of information patients received and the amount they desired, but overestimated both the amount of actual patient participation in decision making and their patients' desire to make decisions. The authors suggest that, in view of these discrepancies, physicians and patients should engage in direct discussion of their preferences.
Phytosetrogens have a potentially adverse effect on coronary vasodilator (endothelial independent) function in women with suspected ischemia: a report from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE) study
Authors: B.Delia Johnson, Susan P. McGorray, Carl J. Pepine, Gregory O. von Mering, Sheryl F. Kelsey, Richard A. Kerensky, Gerald Pohost, William J. Rogers, Nathaniel Reichek, Steven E. Reis, George Sopko, C.Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2002)
ERCC2/XPD Lys751Gln and Asp312Asn Gene Polymorphism and Lung Cancer Risk: A Meta-Analysis Involving 22 Case–Control Studies
Authors: Ping Zhan, Qin Wang, Shu-Zhen Wei, Jing Wang, Qian Qian, Li-Ke Yu, Yong Song
Journal: Journal of Thoracic Oncology (2010)
Council will be able to appeal against "too lenient" decisions by GMC
Authors: C. Dyer
Journal: BMJ (2003)

A new power to appeal to the courts against “too lenient” penalties imposed by the General Medical Council and other healthcare regulatory bodies will probably be used in only a handful of cases a year, the Council for the Regulation of Healthcare Professionals (CRHP) has said.

The CRHP, which came into being in April 2003, is an independent body overseeing nine healthcare regulators, including the GMC. The act that set it up, the National Health Service Reform And Health Care Professions Act, gives it the power to refer decisions …
CERTAIN ASPECTS OF TYROSINE METABOLISM IN THE YOUNG. I. THE DEVELOPMENT OF THE TYROSINE OXIDIZING SYSTEM IN HUMAN LIVER 1
Authors: Norman Kretchmer, S. Z. Levine, Helen McNamara, Henry L. Barnett
Journal: Journal of Clinical Investigation (1956)

The major pathway for tyrosine catabolism in the animal is the non-oxidative transamination of tyrosine to p-hydroxyphenylpyruvate and its subsequent oxidation to homogentisate. The homogentisate is oxidized to fumarylacetoacetate (maleylacetoacetate), which is finally hydrolyzed to fumarate (malate) and acetoacetate. The enzyme system responsible for this catabolism, tentatively called the tyrosine oxidizing system, is soluble and a partial purification can be accomplished with high speed centrifugation of homogenates of liver (1) and kidney (2). When these preparations are used it has been observed (3) that one mole of tyrosine will be completely oxidized to one mole of acetoacetate and one mole of fumarate, with the utilization of two moles of oxygen. In order to obtain maximal tyrosine
Mutations in <i>STAP1</i> Are Associated With Autosomal Dominant Hypercholesterolemia
Authors: Sigrid W. Fouchier, Geesje M. Dallinga-Thie, Joost C.M. Meijers, Noam Zelcer, John J.P. Kastelein, Joep C. Defesche, G. Kees Hovingh
Journal: Circulation Research (2014)

Autosomal-dominant hypercholesterolemia (ADH) is characterized by elevated low-density lipoprotein cholesterol levels and increased risk for coronary vascular disease. ADH is caused by mutations in the low-density lipoprotein receptor, apolipoprotein B, or proprotein convertase subtilisin/kexin 9. A number of patients, however, suffer from familial hypercholesterolemia 4 (FH4), defined as ADH in absence of mutations in these genes and thereafter use the abbreviation FH4.To identify a fourth locus associated with ADH.Parametric linkage analysis combined with exome sequencing in a FH4 family resulted in the identification of the variant p.Glu97Asp in signal transducing adaptor family member 1 (STAP1), encoding signal transducing adaptor family member 1. Sanger sequencing of STAP1 in 400 additional unrelated FH4 probands identified a second p.Glu97Asp carrier and 3 additional missense variants, p.Leu69Ser, p.Ile71Thr, and p.Asp207Asn. STAP1 carriers (n=40) showed significantly higher plasma total cholesterol and low-density lipoprotein cholesterol levels compared with nonaffected relatives (n=91).We mapped a novel ADH locus at 4p13 and identified 4 variants in STAP1 that associate with ADH.
Role of police surgeons is changing
Authors: H. D. L. H. Davies, M. M Stark
Journal: BMJ (1996)

EDITOR,—Graham Moon and colleagues highlight the importance of the further development of Britain's police surgeon service.1 The work of the forensic physician (this is now the preferred term for a doctor providing medical care and forensic assessment of detainees in police stations) has changed dramatically over recent years. Since the introduction of the Police and Criminal Evidence Act 1984 the traditional role of a doctor (attending the police station to take blood in drink-drive cases) has …
Simultaneous Occurrence of Hepatic Adenoma and Focal Nodular Hyperplasia: Report of a Case and Review of the Literature
Authors: Lawrence S. Friedman, David L. Gang, Stephen E. Hedberg, Kurt J. Isselbacher
Journal: Hepatology (1984)

We report the case of a 28-year-old woman with a history of oral contraceptive use and the simultaneous occurrence of histologically proven hepatic adenoma and focal nodular hyperplasia. A review of the literature discloses that the simultaneous occurrence of these hepatic lesions is a rare event. Epidemiologic evidence suggests that hepatic adenomas are etiologically related to oral contraceptive use, whereas focal nodular hyperplasia does not seem to be caused by these agents. The finding of the two lesions in the same liver may represent the chance occurrence of two rare diseases.
Psychodynamic, Time-Limited Group Therapy in Rheumatic Disease &amp;ndash; a Controlled Study with Special Reference to Alexithymia
Authors: Annette Poulsen
Journal: Psychotherapy and Psychosomatics (1991)

Forty-six female patients with rheumatoid arthritis or primary SjÖgren's syndrome participated in a prospective, controlled study of psychodynamic, time-limited group therapy. The paper concentrates on the qualitative outcome evaluated according to the patients' perceptions of what was appreciated as being most helpful in the group. Yalom's 'curative factors Q-sort' served as parameter of effect. Special attention will be given to the prevalence of alexithymia in rheumatic patients, and to the possibilities of ameliorating alexithymic features through group therapy.
Hypericum extract versus imipramine or placebo in patients with moderate depression: randomised multicentre study of treatment for eight weeks Commentary: Has hypericum found its place in antidepressant treatment?
Authors: M. Philipp, R. Kohnen, K.-O Hiller, K. Linde, M. Berner
Journal: BMJ (1999)

Hydroxytyrosol (HOTYR) and tyrosol (TYR), main phenolic compounds of olive oil, have been reported to contribute to the prevention of cardiovascular diseases due to their antioxidant activities, e.g., protection of low-density lipoprotein (LDL) oxidation. Their bioavailability in humans is poor, and they are found in biological fluids mainly as conjugated metabolites. Low concentrations of free phenols are unlikely to explain the biological activities seen in humans after olive oil intake. In this context, antioxidant activities of conjugated metabolites, in a range of concentrations compatible with their dietary consumption, were evaluated. Concentrations of metabolites and their core compounds were estimated in an intervention study of 11 healthy volunteers whose diet was supplemented with 50 ml of virgin olive oil, using high-performance liquid chromatography coupled to mass spectrometry for the simultaneous analysis of 3′-<i>O</i>- and 4′-<i>O</i>-HOTYR-glucuronides and 4′-<i>O</i>-glucuronides of TYR and homovanillyl alcohol in human urine. Glucuronides and core compounds were tested for their chemical (hydrogen donation by 1,1-diphenyl-2-picrylhydrazyl free radical test) and in vitro biological (inhibition of Cu-mediated LDL oxidation) antioxidant activities at the concentration ranges observed in human biological fluids (range, 0.01–10 μM) after dietary olive oil consumption. None of the glucuronides displayed significant antioxidant activities at the concentrations tested.