tbuckley/cabot-search huggingface dataset:
Estimating the Exposure–Response Relationships between Particulate Matter and Mortality within the APHEA Multicity Project
Authors: Evangelia Samoli, Antonis Analitis, Giota Touloumi, Joel Schwartz, Hugh R. Anderson, Jordi Sunyer, Luigi Bisanti, Denis Zmirou, Judith M. Vonk, Juha Pekkanen, Pat Goodman, Anna Paldy, Christian Schindler, Klea Katsouyanni
Journal: Environmental Health Perspectives (2004)

Several studies have reported significant health effects of air pollution even at low levels of air pollutants, but in most of theses studies linear nonthreshold relations were assumed. We investigated the exposure-response association between ambient particles and mortality in the 22 European cities participating in the APHEA (Air Pollution and Health--A European Approach) project, which is the largest available European database. We estimated the exposure-response curves using regression spline models with two knots and then combined the individual city estimates of the spline to get an overall exposure-response relationship. To further explore the heterogeneity in the observed city-specific exposure-response associations, we investigated several city descriptive variables as potential effect modifiers that could alter the shape of the curve. We conclude that the association between ambient particles and mortality in the cities included in the present analysis, and in the range of the pollutant common in all analyzed cities, could be adequately estimated using the linear model. Our results confirm those previously reported in Europe and the United States. The heterogeneity found in the different city-specific relations reflects real effect modification, which can be explained partly by factors characterizing the air pollution mix, climate, and the health of the population.
Abstract 3071: Size-based isolation of circulating tumor cells (CTCs) in mouse tumor models
Authors: Katarina Kolostova, Robert M. Hoffman, Ali Maawy, Yong Zhang, Vladimir Bobek
Journal: Cancer Research (2014)

Abstract We report here isolation and cultivation of circulating tumor cells (CTCs) in five human epithelial cancers (lung, prostate, colon, pancreatic and breast cancer) implanted in nude mice. All of the cancer cells were labeled with green fluorescent protein (GFP) for detection. CTCs were isolated with an antigen-independent size-based separation device (MetaCell®, Metacell s.r.o., Ostrava, Czech Republic). We were able to capture on average more than 2 cells for each of above cancer types whereby the tumor has been implanted atleast 2 weeks before blood withdrawal. The number of CTC is dependent on the stage of tumor in animals. There was a very high heterogeneity of the CTCs with regard to cell size and cell phenotype including epithelial- and mesenchymal-like type cells in vitro. The development of a facile in vitro isolation and imaging technology for CTCs will enable deeper understanding of CTC biology. Citation Format: Katarina Kolostova, Robert M. Hoffman, Ali Maawy, Yong Zhang, Vladimir Bobek. Size-based isolation of circulating tumor cells (CTCs) in mouse tumor models. [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 3071. doi:10.1158/1538-7445.AM2014-3071
Abstract 3255: Single oral dose pharmacokinetics of cancer chemopreventive phytochemicals from <i>Angelica gigas</i> Nakai in men and women
Authors: Jinhui Zhang, Li Li, Thomas W. Hale, Wayne Chee, Chengguo Xing, Cheng Jiang, Junxuan Lü
Journal: Cancer Research (2014)

Abstract The ethanol extracts of the root of Korean herb Angelica gigas Nakai (AGN) have promising anti-cancer, anti-nociceptive and other activities in rodent models. It is currently believed that the pyranocoumarin decursin and its structural isomer decursinol angelate (DA) in such extracts contribute to the in vitro anti-cancer activity. We and others have demonstrated that both decursin and DA were extensively converted to decursinol (DOH) in rodents. However, our in vitro experiments using human and rodent S9 fractions suggested the hypothesis that decursin and/or DA might be metabolized differently in humans. Given the notable difference in the biological activities between decursin/DA and DOH, we conducted a single oral dose pharmacokinetic study of these phytochemicals in healthy volunteers to address a key question for human translatability of preclinical animal studies of decursin, DA or AGN extract. Knowing that chemicals other than decursin and DA in AGN had minimal effect on their absorption and metabolism in rodents, we used an AGN-based dietary supplement as the study drug in compliance with the FDA and institutional requirements. In all, 20 healthy subjects (10 men and 10 women) had completed the study in full. AGN product was very well tolerated by all subjects as evidenced by plasma biochemistry, complete blood cell count and physical examination. Analyzing plasma samples using UHPLC-MS/MS showed that, though humans metabolized DA slightly slower than rodents, both decursin and DA were extensively converted to DOH. Gender and racial/ethnicity do not appear to dramatically affect the PK parameters. Since we show here that humans metabolize decursin and DA in similar pattern with rodents, the anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarker data generated in rodent models will likely be relevant for human translation. In spite of the limited number of healthy individuals in the trial, this project demonstrated feasibility for our team to consider translational research in disease-oriented populations. Citation Format: Jinhui Zhang, Li Li, Thomas W. Hale, Wayne Chee, Chengguo Xing, Cheng Jiang, Junxuan Lü. Single oral dose pharmacokinetics of cancer chemopreventive phytochemicals from Angelica gigas Nakai in men and women. [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 3255. doi:10.1158/1538-7445.AM2014-3255
Research in Health Care
Authors: H. T. Sorensen
Journal: BMJ (1996)

I K Crombie with H T O Davies Wiley, £14.99, pp 302 ISBN 0 471 96259 7

The aim of research in health care is to improve the quality of health services as well as the use of resources. Not much attention was given to these problems a few decades ago, but health services research has become increasingly important. It deals with the health sector, its functions and services, and the health …
Points: Guidelines for community menopausal clinics
Authors: A. Mills
Journal: BMJ (1983)

write: Dr Lightman (6 August, p 422) has missed the point.We were not reviewing the variety of lesions that might provoke hot flushes.The object of our case presentation (23 July, p 262) was the objective demonstration that climacteric flushing in a man was associated with circulatory responses virtually identical to those we had shown during the meno- pausal hot flush.'Every blush is not a flush, however, and until the phenomena reported in different circumstances in either sex are recorded by tech- niques capable of following the rapid circulatory changes that occur during the hot flush our under- standing of the mechanisms responsible for the menopausal hot flush will remain obscure.
A laboratory running test: metabolic responses of sprint and endurance trained athletes.
Authors: M E Cheetham, C Williams, H K Lakomy
Journal: British Journal of Sports Medicine (1985)

A laboratory-based sprint running test has been devised to examine the performance characteristics and metabolic responses of an individual to 30 seconds of maximal exercise. A non-motorised treadmill was used so that the individual was able to sprint at his own chosen speed and also to vary his speed as fatigue occurred. The treadmill was instrumented so that the chosen speeds as well as the equivalent distance travelled could be monitored by micro-computer throughout the test. The test-retest reliability of the procedure was investigated with 14 recreational runners who performed the test on different days. A good correlation (r = 0.93) was found between the values obtained for peak running speeds on the two occasions. In an attempt to establish whether or not this test could be used to identify the differences in the performance characteristics of highly trained individuals, the responses to the test of eleven sprint trained and eleven endurance trained athletes were examined. The sprint trained athletes covered a greater distance (162.2 +/- 5.95 m vis 153.51 +/- 12.32 m; p less than 0.01) and had higher blood lactate concentrations (16.52 +/- 1.23 mM vis 12.98 +/- 1.77 mM; p less than 0.01) than the endurance trained athletes. Therefore this laboratory sprint running test offers an additional way of investigating human responses to brief periods of high intensity exercise.
Italian police arrest drug agency officials over alleged falsification of data
Authors: Michael Day
Journal: BMJ (2008)

A scandal involving drug licences for cash has engulfed Italy’s drug regulatory agency, and leading officials have been arrested, along with people linked to major drug companies.

The most senior figure to have been arrested and held by the police in his own home (“arresto al domiciliaro”) is Pasqualino Rossi, vice president of the Agenzia Italiana del Farmaco (AIFA), the Italian Agency for Pharmaceuticals. Dr Rossi is also one of Italy’s most senior representatives at the European Medicines Agency (EMEA).

Six drug company lobbyists have also been held. As the BMJ went to press, four people were in custody and three were under house arrest. Another individual wanted by the police was not …
Usefulness of a low-dose intravenous immunoglobulin regimen for the treatment of thrombocytopenia associated with AIDS
Authors: Abraham Majluf-Cruz, Germán Luna-Castaños, Soledad Huitrón, Leopoldo Nieto-Cisneros
Journal: American Journal of Hematology (1998)

Infection with the human immunodeficiency virus (HIV) frequently is complicated with thrombocytopenia (HIV-Thr) during all stages of the infection. The treatments for autoimmune thrombocytopenic purpura (ITP) are used in HIV-Thr; however, their effects upon the immune status of patients with acquired immunodeficiency syndrome (AIDS) are unknown. Intravenous immunoglobulin (IVIg) is used in patients with ITP and HIV-Thr; however, its usefulness in thrombocytopenic AIDS patients has not been directly addressed. We used a low-dose IVIg regimen (0.04 g/kg per week during five weeks) for the treatment of HIV-Thr complicating AIDS. Thirteen patients received IVIg. We observed a response to IVIg in 13 patients by the end of week one and in 10 patients by the end of week five. Long-term response, evaluated three months after stopping IVIg, was present in four cases. IVIg was well tolerated and no opportunistic infections were observed during the study period. Compared with previous reports, we used 10% of the previously proposed dosage with an important decrease in the cost of treatment. Our results suggest that this low-dose IVIg regimen is a highly effective, nonexpensive alternative in treating HIV-Thr in AIDS. If sustained responses can be obtained with a similar low-dose maintenance regimen, IVIg may be the first choice for the treatment of HIV-Thr in AIDS patients.
Downregulation of glutathione S-transferase pi in asthma contributes to enhanced oxidative stress
Authors: Kathy T. Schroer, Aaron M. Gibson, Umasundari Sivaprasad, Stacey A. Bass, Mark B. Ericksen, Marsha Wills-Karp, Tim LeCras, Anne M. Fitzpatrick, Lou Ann S. Brown, Keith F. Stringer, Gurjit K. Khurana Hershey
Journal: Journal of Allergy and Clinical Immunology (2011)
A neural basis for the Chorus model?
Authors: M. J. Tovée
Journal: Behavioral and Brain Sciences (1998)

The neural basis of the Chorus model has been cast in terms of the visual alphabet theory, but the neural evidence can also be interpreted as supporting a theory of higher level representation in which neurons are responsive to complex 3D stimuli. These neurons, functioning as a population, could also form the basis of a representation such as envisaged by the Chorus model.
Abstract A12: Chromatin accessibility reveals insight into androgen receptor activation and transcriptional specificity
Authors: Alok Tewari, Galip Yardimci, Yoichiro Shibata, Nathan Sheffield, Lingyun Song, Barry Taylor, Gerhard Coetzee, Terrence Furey, Gregory Crawford, Phillip Febbo
Journal: Cancer Research (2012)

Abstract Epigenetic mechanisms such as chromatin accessibility and histone modifications impact transcription factor binding to DNA and transcriptional specificity. The androgen receptor (AR), a master regulator of prostate cancer initiation and progression, acts primarily through ligand-activated transcription of target genes. By combining deep sequencing with DNase I hypersensitivity analysis (DNase-seq) and RNA analysis (mRNA-seq) we assessed genome-wide chromatin structure and transcription and combined this data with publicly available AR chromatin immunoprecipitation data (AR ChIP-seq). We find that 72% of DNase I hypersensitive sites (DHS) overlap each other before and after androgen in LNCaP cells. Interestingly, in regions of increased chromatin accessibility with androgen induction, the canonical AR DNA recognition motif is enriched. Comparing identified DHS to AR binding sites from three different data sets consistently reveals that 50% of AR binding overlaps a DHS in induced cells. Of those sites with both DHS and AR binding, approximately half are available prior to androgen induction (i.e., “primed”) and half open in response to androgen stimulation. This contrasts with the glucocorticoid receptor (GR), which was recently reported to bind to DNA primarily in regions that are accessible to nuclease cleavage prior to ligand activation. Our mRNA-seq analysis discovered 339 genes regulated by AR activation (FDR &amp;lt; 0.05), including 16 of the 19 most commonly identified AR-mediated genes in several other studies. Importantly, we find that regions of increased chromatin accessibility are significantly associated with genes identified as AR-regulated by mRNA-seq. Finally, base pair resolution of the DNase-seq signal reveals distinct footprinting patterns associated with the AR-DNA interaction. Analysis of chromatin structure, AR binding, and transcription prior to and following androgen induction demonstrates that AR activation by ligand induces genome-wide changes in chromatin accessibility, these changes correspond to AR binding to the genome, and they impact AR-mediated transcriptional response. These findings suggest that interaction between the AR and DNA alters chromatin structure and transcriptional specificity. Citation Format: Alok Tewari, Galip Yardimci, Yoichiro Shibata, Nathan Sheffield, Lingyun Song, Barry Taylor, Gerhard Coetzee, Terrence Furey, Gregory Crawford, Phillip Febbo. Chromatin accessibility reveals insight into androgen receptor activation and transcriptional specificity [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 A12.
Spatial and temporal patterns of gene expression for the proteoglycans biglycan and decorin and for transforming growth factor-β1 revealed byin situ hybridization during experimentally induced liver fibrosis in the rat
Authors: Nora B. Krull, Thomas Zimmermann, Axel M. Gressner
Journal: Hepatology (1993)

Expression of the proteoglycans biglycan and decorin and of transforming growth factor-beta 1 at various stages of liver fibrosis induced experimentally in rats by oral administration of thioacetamide was examined. Using in situ hybridization combined with immunocytochemical staining for cell-type characteristic markers, we demonstrate spatial and temporal expression patterns specific for each of the genes. Biglycan gene expression levels coincided tightly with the activity and extent of fibrosis, fat-storing cells and their transformed form, the myofibroblast-like cells, being the major contributors. Decorin messenger RNA was detectable only after the transition to the chronic inflammatory stage in nonparenchymal cells of periportal fields and, transiently, in the forming septa. In the cirrhotic stage, expression was detected solely in periportal fields with enhanced bile duct proliferation. Transforming growth factor-beta 1 expression was undetectable in normal liver. During the subacute inflammatory stage, a hepatocyte subpopulation expressing low levels of transforming growth factor-beta 1 occurred at the limiting plate. With the progression of fibrosis, transforming growth factor-beta 1 expression levels increased considerably but remained restricted to the mesenchymal cells of the fibrotic septa.
"Comparably Massive" Penicillin G Therapy in Renal Failure
Authors: CHARLES S. BRYAN
Journal: Annals of Internal Medicine (1975)

Impairment of penicillin G excretion in renal failure may result in life-threatening, dose-related toxicity. We report a method for achieving a desired mean serum penicillin G concentration in patients with renal failure, with minimal risk of both undertreatment and drug toxicity. The method is based on the linear relation between the total plasma clearance of penicillin G (Cpen) and the endogenous creatinine clearance. The daily maintenance dose of penicillin G (units) is defined by the product, Cpen (ml/min) X desired mean serum penicillin G concentration (µg/ml) X 2300. Application of this method to patients with various degrees of renal impairment by either constant-rate infusion or intermittent infusion gave serum penicillin G concentrations within the desired range in all but 1 of 15 instances. On the basis of these observations, practical guidelines for "comparably massive" penicillin G therapy are suggested.
A Serum Factor in Lupus Erythematosus with Affinity for Tissue Nuclei
Authors: E. J. Holborow, D. M. Weir, G. D. Johnson
Journal: BMJ (1957)

SYSTEMIC LUPUS ERYTHEMATOSUSBRrsin 47 cases by the finding of L.E. cells (with necropsy confirmation in seven), in one by typical changes at necropsy, and in one by skin biopsy.For help in providing clinical material I am particularly in- debted to Dr. Stewart Barber, who generously gave me access to his cases.
Carcinogen Metabolism and Human Cancer
Authors: A. H. Conney
Journal: New England Journal of Medicine (1973)

The human population is exposed to numerous chemical carcinogens in the environment, and it is believed that many human cancers are caused by exposure to these chemicals. Examples of carcinogens in our environment include benzo[a]pyrene (BP) and other polycyclic aromatic hydrocarbons in cigarette smoke, polluted city air and charcoal-broiled meat, aflatoxin in moldy foods and nitrosamines in certain meats treated with nitrite. The first example of an effect of environmental chemicals on the incidence of cancer in man was described in 1775 by Percivall Pott, who noted the occurrence of a high incidence of scrotal cancer in chimney sweeps in . . .
Hemoglobin potentiates central nervous system damage.
Authors: S M Sadrzadeh, D K Anderson, S S Panter, P E Hallaway, J W Eaton
Journal: Journal of Clinical Investigation (1987)

Iron and iron compounds--including mammalian hemoglobins--catalyze hydroxyl radical production and lipid peroxidation. To determine whether hemoglobin-mediated lipid peroxidation might be important in hemorrhagic injuries to the central nervous system (CNS), we studied the effects of purified hemoglobin on CNS homogenates and injected hemoglobin into the spinal cords of anesthetized cats. Hemoglobin markedly inhibits Na/K ATPase activity in CNS homogenates and spinal cords of living cats. Hemoglobin also catalyzes substantial peroxidation of CNS lipids. Importantly, the potent iron chelator, desferrioxamine, blocks these adverse effects of hemoglobin, both in vitro and in vivo. Because desferrioxamine is not known to interact with heme iron, these results indicate that free iron, derived from hemoglobin, is the proximate toxic species. Overall, our data suggest that hemoglobin, released from red cells after trauma, can promote tissue injury through iron-dependent mechanisms. Suppression of this damage by desferrioxamine suggests a rational therapeutic approach to management of trauma-induced CNS injury.
Evaluation of N-acetylcysteine and methylprednisolone as therapies for oxygen and acrolein-induced lung damage.
Authors: J A Critchley, J M Beeley, R J Clark, M Summerfield, S Bell, M S Spurlock, J A Edginton, J D Buchanan
Journal: Environmental Health Perspectives (1990)

Reactive oxidizing species are implicated in the etiology of a range of inhalational pulmonary injuries. Consequently, various free radical scavengers have been tested as potential prophylactic agents. The sulfydryl compound, N-acetylcysteine (NAC) is the only such compound clinically available for use in realistic dosages, and it is well established as an effective antidote for the hepatic and renal toxicity of paracetamol. Another approach in pulmonary injury prophylaxis is methylprednisolone therapy. We evaluated NAC and methylprednisolone in two rat models of inhalational injury: 40-hr exposure to greater than 97% oxygen at 1.1 bar and 15-min exposure to acrolein vapor (210 ppm). For oxygen toxicity, NAC (80 mg) or methylprednisolone (10 mg) were given IP every 2 or 6 hr, respectively. For acrolein, single doses of NAC (1 g/kg) and methylprednisolone (30 mg/kg) were given intravenously 15 min before exposure. In sham-exposed control animals, neither treatment favorably effected mortality, lung wet/dry weight ratios, or pulmonary histology. The increases in lung wet/dry weight ratios, seen with both oxygen and acrolein toxicity were reduced with both treatments. However, with oxygen, NAC therapy was associated with considerably increased mortality and histological changes. Furthermore, IP NAC administration resulted in large volumes of ascitic fluid. With acrolein, IV, NAC had no significant effect on mortality or pulmonary histological damage. Methylprednisolone had no beneficial effects on either the mortality or histological damage observed in either toxicity model. We caution against the ad hoc use of NAC in the management of inhalational pulmonary injury.
"A CASE OF PHARYNGEAL DIPHTHERIA PROBABLY DUE TO AUTO-INFECTION FROM A DIPHTHERIC LESION OF THE THUMB"
Authors: George H. Weaver
Journal: JAMA (1923)

<h3>To the Editor:</h3> —The report by Baldwin, McCallum and Doull (The Journal, May 12, p. 1375) of a case of pharyngeal diphtheria, probably due to auto-infection from a diphtheric lesion of the thumb, recalls a case that occurred in Durand Hospital, reported by Emge (The Journal, Aug. 7, 1915, p. 529). In this case an intern received an injury to his finger while performing an intubation for laryngeal diphtheria. The infection of the finger preceded the throat infection several days.