tbuckley/cabot-search huggingface dataset:
The relation of price of antiretroviral drugs and foreign assistance with coverage of HIV treatment in Africa: retrospective study
Authors: E. Bendavid, E. Leroux, J. Bhattacharya, N. Smith, G. Miller
Journal: BMJ (2010)

To determine the association of reductions in price of antiretroviral drugs and foreign assistance for HIV with coverage of antiretroviral treatment.Retrospective study.Africa.13 African countries, 2003-8.A price index of first line antiretroviral therapy with data on foreign assistance for HIV was used to estimate the associations of prices and foreign assistance with antiretroviral coverage (percentage of people with advanced HIV infection receiving antiretroviral therapy), controlling for national public health spending, HIV prevalence, governance, and fixed effects for countries and years.Between 2003 and 2008 the annual price of first line antiretroviral therapy decreased from $1177 (£733; €844) to $96 and foreign assistance for HIV per capita increased from $0.4 to $13.8. At an annual price of $100, a $10 decrease was associated with a 0.16% adjusted increase in coverage (95% confidence interval 0.11% to 0.20%; 0.19% unadjusted, 0.14% to 0.24%). Each additional $1 per capita in foreign assistance for HIV was associated with a 1.0% adjusted increase in coverage (0.7% to 1.2%; 1.4% unadjusted, 1.1% to 1.6%). If the annual price of antiretroviral therapy stayed at $100, foreign assistance would need to quadruple to $64 per capita to be associated with universal coverage. Government effectiveness and national public health expenditures were also positively associated with increasing coverage.Reductions in price of antiretroviral drugs were important in broadening coverage of HIV treatment in Africa from 2003 to 2008, but their future role may be limited. Foreign assistance and national public health expenditures for HIV seem more important in expanding future coverage.
Abstract 773: Crizotinib (PF-02341066) reverses multidrug resistance in cancer cells by inhibiting the function of P-glycoprotein
Authors: Wen-jing Zhou, Fang Wang, Xu Zhang, Kenneth Kin Wah To, Hong-bing Huang, Li-Wu Fu
Journal: Cancer Research (2012)

Abstract Background and purpose: Besides targeting the well-known oncogenic c-Met, crizotinib is the first oral tyrosine kinase inhibitor (TKI) inhibiting anaplastic lymphoma kinase (ALK) in clinical trials for the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the potential multidrug resistance (MDR) reversal by crizotinib in vitro and in vivo. Experimental approach: MTT methods were used in vitro and the xenografts in nude mice were used in vivo to investigate crizotinib reversal of MDR. To understand the mechanisms for MDR reversal, the alterations of intracellular doxorubicin(Dox) or rhodamine 123 accumulation, Dox effluxion, ABCB1 expression level, ATPase activity of ABCB1, and crizotinib-induced c-Met, Akt and Erk1/2 phosphorylation were examined. Key results: Crizotinib significantly enhanced the cytotoxicity of ABCB1 substrate chemotherapeutic agents in MDR cells, with no effect found on sensitive cells in vitro and in vivo. In addition, crizotinib significantly increased the intracellular accumulation of rhodamine 123 and doxorubicin and inhibited the drug efflux in ABCB1-overexpressing MDR cells. Further studies showed that crizotinib enhanced the ATPase activity of ABCB1 in concentration-dependent manner. However, the expressions of ABCB1 were not affected and the reversal activity of crizotinib was not related to the phosphorylation of c-Met, Akt or Erk1/2. Importantly, crizotinib significantly enhanced the effect of paclitaxel against the KBv200 cell xenografts in nude mice. Conclusions and implications: Crizotinib was found to reverse ABCB1-mediated MDR by inhibiting ABCB1 transport function without involvement of ABCB1 expression or blockade of the Akt or Erk1/2 pathways. These findings is useful for combination chemotherapy of crizotinib with conventional chemotherapeutic drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 773. doi:1538-7445.AM2012-773
De novo mutations in mental retardation
Authors: Joris A Veltman
Journal: Genome biology (2011)

Deep exome resequencing is a powerful approach for delineating patterns of protein-coding variation among genes, pathways, individuals and populations.We analyzed exome data from 2,440 individuals of European and African ancestry as part of the National Heart, Lung, and Blood Institute's Exome Project, the aim of which is to discover novel genes and mechanisms that contribute to heart, lung and blood disorders.Each exome was sequenced to a mean coverage of 116×, allowing detailed inferences about the population genomic patterns of both common variation and rare coding variation.We identifi ed more than 500,000 single nucleotide variations, the majority of which were novel and rare (76% of variants had a minor allele frequency of less than 0.1%), refl ecting the recent dramatic increase in the size of the human population.The unprecedented magnitude of this dataset allowed us to rigorously characterize the large variation in nucleotide diversity among genes (ranging from 0 to 1.32%), as well as the role of positive and purifying selection in shaping patterns of proteincoding variation and the diff erential signatures of population structure from rare and common variation.This dataset provides a framework for personal genomics and is an important resource that will allow inferences of broad importance to human evolution and health.
Mandell, Douglas, and Bennett's principles and practice of infectious diseases
Authors: Alimuddin Zumla
Journal: The Lancet Infectious Diseases (2010)

Infectious diseases are responsible for millions of deaths worldwide every year. News on outbreaks of infectious diseases like Ebola, Marburg, Lassa fever, which have high death rates, are often the focus of exaggerated press scare stories. 30 years ago the prevailing viewpoint in the USA and Europe was that infectious diseases were conquered and had become a problem of the past. This irresponsible and complacent view changed dramatically after the unexpected emergence and rapid spread of the epidemic of HIV/AIDS in the 1990s.
Abstract 3930: Integrative genomic analysis reveals SWI/SNF chromatin remodeling complex to be a TGFβ-mediating tumor suppressor pathway in pancreatic cancer
Authors: Alan H. Shain, Karen Matsukuma, Craig Giacomini, Collins A. Karikari, Manuel Hidalgo, Anirban Maitra, Jonathan R. Pollack
Journal: Cancer Research (2011)

Abstract Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer deaths in the developed world. A more complete characterization of molecular alterations may suggest new avenues for targeted therapy. Here we report the high-resolution genomic and transcriptional profiling of seventy PDAC early-passage tumor xenografts and cell lines – the largest PDAC dataset currently available of this sample size and resolution. Notable among novel loci, genomic deletion/mutation frequently targeted components of the SWI/SNF chromatin remodeling complex, including ARID1A, ARID1B, PBRM1, SMARCA2 and SMARCA4. Overall, focal deletion/mutation of a SWI/SNF component occurred in at least one-third of all PDAC specimens. In cell culture, RNAi-mediated knockdown of SWI/SNF subunits enhanced cell growth, growth-factor independence, and resistance to TGFβ growth-inhibition. Previously, SWI/SNF was reported to mediate TGFβ signaling. Remarkably, we found that five of the top ten SWI/SNF-mediated TGFβ-downregulated genes were focally amplified (MYC, BIRC3, PARD6B, KLF5, and CEBPD), while two of the top ten upregulated genes were focally deleted (PPAP2B, TNC), implying that its role in TGFβ growth-inhibitory signaling drives SWI/SNF loss in PDAC. In summary, we report the SWI/SNF chromatin remodeling complex, likely through mediating TGFβ signaling, to be a major tumour suppressor pathway in PDAC. 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 3930. doi:10.1158/1538-7445.AM2011-3930
Endoscopic Ultrasonography with a Linear-Type Echoendoscope in the Evaluation of 94 Patients with Pancreatobiliary Disease
Authors: M. Giovannini, J. F. Seitz
Journal: Endoscopy (1994)

The purpose of this study was to evaluate a new endoscopic ultrasonography (EUS) device using a curved-array transducer with a 120-degree sagittal scan angle in the diagnosis of pancreatobiliary disease. From October 1991 to June 1993, 94 patients underwent EUS to assess radiologically detected anomalies (62 cases), tumors of the papilla of Vater (seven cases) and laboratory findings demonstrating cholestasis of unexplained origin (25 cases). In 41 cases, surgery was performed after EUS, and in 40 cases ERCP was also performed. The EUS diagnosis of chronic calcifying pancreatitis was confirmed by ERCP in 14 of 18 patients. In 30 cases, EUS detected a pancreatic tumor. In 26 of these patients, surgery was performed, confirming EUS findings regarding tumor size, portal, mesenteric, and splenic invasion, and lymph-node involvement in 20 of 25 pancreatic carcinomas (80%). In five of seven patients in whom EUS detected ampullary carcinoma, cephalic duodenopancreatectomy was performed, and the histology of the surgical specimen confirmed the diagnosis in all five. In 25 patients presenting with cholestasis of unexplained origin, EUS provided the diagnosis in 22 cases (88%). EUS using a curved-array transducer appears to be an effective diagnostic method for pancreatobiliary lesions. These results should be further evaluated in a larger series of patients.
β1 and β2-adrenergic receptor subtype effects in German shepherd dogs with inherited lethal ventricular arrhythmias
Authors: E Sosunov
Journal: Cardiovascular Research (2000)

Objective: Delayed afterdepolarization-induced triggered activity originating in ventricular myocardium is a mechanism for some age-dependent, inherited ventricular tachycardias in a colony of German shepherd dogs. Methods: We used standard microelectrode techniques to study β-adrenergic receptor subtype modulation of the triggered activity in anteroseptal left ventricular myocardium from eleven of these dogs and seven unafflicted, age-matched German shepherd controls. Results: During sustained stimulation at cycle lengths of 300–4000 ms, 10−9–10−7 M isoproterenol concentration-dependently shortened action potential duration (APD) to 90% repolarization more in myocardium from afflicted than from unafflicted dogs. This shortening was prevented by a β1-blocker CGP20712A (10−7 M) while a β2-blocker ICI118551 (10−7 M) did not modify the effect of isoproterenol in either group. The β2-agonist zinterol 10−8–10−6 M had no effect on APD. Stimulation at a cycle length of 250 ms in the presence of 10−7 M isoproterenol induced more triggered AP in myocardium from afflicted than unafflicted dogs. β1-Blockade completely eliminated, while β2-blockade facilitated, and the β2-agonist zinterol did not induce triggered activity in the two groups. Conclusion: Isoproterenol effects on APD and triggered activity in the myocardium of dogs with inherited arrhythmias are due primarily to an abnormality of β1-adrenoceptor mediated signaling that is subject to β2-adrenergic modulation.
JAK2 and MPL protein levels determine TPO-induced megakaryocyte proliferation vs differentiation
Authors: Rodolphe Besancenot, Damien Roos-Weil, Carole Tonetti, Hadjer Abdelouahab, Catherine Lacout, Florence Pasquier, Christophe Willekens, Philippe Rameau, Yann Lecluse, Jean-Baptiste Micol, Stefan N. Constantinescu, William Vainchenker, Eric Solary, Stéphane Giraudier
Journal: Blood (2014)
Cascades, Collusions, and Conflicts in Cardiology
Authors: Thomas N. James
Journal: JAMA (1988)

For many valid reasons, no physician today can afford to ignore the question of cost of health care. One of the more compelling reasons why this is true is that such costs have soared so rapidly that they have understandably become a target for control by the government, industry, and all others who primarily pay the bill. During this period of growing concern and increasing efforts to control the cost of medical care, it is crucially important that the quality of care not be eroded and that access to care not be limited unfairly. See also p 2419. In this issue ofTHE JOURNAL, Sawitz et al<sup>1</sup>of San Francisco report that during a decade when hospitalization time for patients with acute myocardial infarction decreased significantly, physician services tripled. They properly concluded that it was not possible to determine whether those services and the diagnostic information obtained may have
Cardiospecific Overexpression of the Prostaglandin EP <sub>3</sub> Receptor Attenuates Ischemia-Induced Myocardial Injury
Authors: Melanie Martin, Jutta Meyer-Kirchrath, Gernot Kaber, Christoph Jacoby, Ulrich Flögel, Jürgen Schrader, Ulrich Rüther, Karsten Schrör, Thomas Hohlfeld
Journal: Circulation (2005)

The generation of prostaglandin E2 (PGE2) is significantly increased in acute myocardial ischemia and reperfusion. PGE2, in addition to other prostaglandins, protects the reperfused ischemic myocardium. It has been hypothesized that this cardioprotection is mediated by E-type prostaglandin receptors of the Gi-coupled EP3 subtype.We tested this hypothesis by generating transgenic (tg) mice with cardiospecific overexpression of the EP3 receptor. According to ligand binding, a 40-fold overexpression of the EP3 receptor was achieved in membranes prepared from tg hearts compared with wild-type (wt) littermates. In isolated cardiomyocytes from tg mice, the forskolin-induced rise in cAMP was markedly attenuated, indicating coupling of the overexpressed EP3 receptor to inhibitory G proteins (Gi) with constitutive receptor activity. There was no evidence for EP3 receptor coupling to Gq-mediated protein kinase C signaling. Isolated hearts from tg and wt mice were subjected to 60 minutes of no-flow ischemia and 45 minutes of reperfusion. In tg hearts, ischemic contracture was markedly delayed compared with wt hearts, and the ischemia-induced increase in left ventricular end-diastolic pressure was reduced by 55%. Creatine kinase and lactate dehydrogenase release was significantly decreased by 85% and 73%, respectively, compared with wt hearts.Constitutive prostaglandin EP3 receptor signaling exerts a protective effect on cardiomyocytes, which is probably Gi mediated and results in a remarkable attenuation of myocardial injury during ischemia and reperfusion. Cardioprotective actions of E-type prostaglandins may be mediated by this receptor subtype.
Ethanol Potentiation of Aspirin-Induced Prolongation of the Bleeding Time
Authors: Daniel Deykin, Paul Janson, Louise McMahon
Journal: New England Journal of Medicine (1982)

THE template bleeding time is a sensitive and reproducible measure of primary hemostasis. It is influenced by platelet function and vascular tone, as well as by platelet number.1 Usually after a normal subject ingests 325 mg of aspirin the bleeding time is moderately prolonged, reaching its peak of approximately twice base-line values within 12 hours and returning to approximately base-line levels by 24 hours. In two subjects who had taken 325 mg of aspirin we observed a second rise in the bleeding time — at 36 hours after ingestion in one and 60 hours in the other — to levels . . .
PREVENTION OF BLOOD CLOTTING BY DAKIN'S SODIUM HYPOCHLORITE SOLUTION
Authors: T. S. Githens
Journal: JAMA (1918)

I fear is far from the truth, especially in this part of the country.I wish you really knew how much there is going on along this line.Enclosed are a few cuttings; these are absolutely authentic reports from head- quarters.If it stopped at ground glass it might be easy; but steel filings, stone, sand of a very irritating kind, aluminum or wire filings, and brassy metal powders have all been found,
Library and Information Services for Small Hospitals
Authors: Kelly M. West
Journal: JAMA (1975)

The quality of medical care is dependent on effective and expeditious information services for physicians and other health workers. Small hospitals have been at a particular disadvantage in this respect, mainly because unit costs of library services have been quite high when delivered on a small scale with traditional resources and methods. The importance of this problem is suggested by the fact that more than half of US hospitals have less than 100 beds, and that library services have been primitive or nonexistent in most of these institutions. Certain recent developments will permit most of these smaller hospitals to provide creditable information services at modest cost. (<i>JAMA</i>232:505-508, 1975)
Successful treatment of anogenital Bowen's disease with the immunomodulator imiquimod, and monitoring of therapy by DNA image cytometry
Authors: R. Gutzmer, M. Kaspari, M. Vogelbruch, P. Kiehl, A. Kapp, T. Werfel, J-P. Brodersen
Journal: British Journal of Dermatology (2002)

Journal Article Successful treatment of anogenital Bowen's disease with the immunomodulator imiquimod, and monitoring of therapy by DNA image cytometry Get access R. Gutzmer, R. Gutzmer Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, D‐30449 Hannover, Germany Ralf Gutzmer. E‐mail: rgutzmer@gmx.de Search for other works by this author on: Oxford Academic Google Scholar M. Kaspari, M. Kaspari Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, D‐30449 Hannover, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Vogelbruch, M. Vogelbruch Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, D‐30449 Hannover, Germany Search for other works by this author on: Oxford Academic Google Scholar P. Kiehl, P. Kiehl Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, D‐30449 Hannover, Germany Search for other works by this author on: Oxford Academic Google Scholar A. Kapp, A. Kapp Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, D‐30449 Hannover, Germany Search for other works by this author on: Oxford Academic Google Scholar T. Werfel, T. Werfel Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, D‐30449 Hannover, Germany Search for other works by this author on: Oxford Academic Google Scholar J‐P. Brodersen J‐P. Brodersen Department of Dermatology and Allergology, Hannover Medical University, Ricklinger Str. 5, D‐30449 Hannover, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 1, 1 July 2002, Pages 160–165, https://doi.org/10.1046/j.1365-2133.2002.04729.x Published: 01 July 2002 Article history Accepted: 08 December 2001 Published: 01 July 2002
INTRACELLULAR LOCALIZATION OF TYROSINASE INHIBITOR IN AMELANOTIC AND MELANOTIC MALIGNANT MELANOMA
Authors: TOSHIO HAMADA, YUTAKA MISHIMA
Journal: British Journal of Dermatology (1972)

Summary.— Intracellular distribution of the tyrosinase inhibitor in malignant melanoma cells has been investigated in order to elucidate the defect of melanization in the pigment cell cytoplasm and premelanosomes of amelanotic melanoma. We have found that the tyrosinase inhibitor has its highest activity in the cytoplasmic soluble fraction for both amelanotic and melanotic melanomata. However, inhibitor assay of melanoma subfractions reveals a distinct difference between the inhibitor activity of amelanotic and melanotic melanomata. Premelanosome‐containing subfractions of amelanotic melanomata contain much higher inhibitor activity than those of melanotic malignant melanomata. A high concentration of inhibitor seen in subfraction 3 which contains most of the total succinoxidase activity is found to be contained in the premelanosomes of this subfraction. It is suggested that the absence of melanization in the non‐premelanosomal cytoplasm of pigment cells and in the premelanosomes of tyrosinase containing amelanotic melanomata is directly related to the concentration of tyrosinase inhibitor in these compartments of the cells.
MANIC-DEPRESSIVE INSANITY AND VISCERAL DISEASE.
Authors: HENRY S. UPSON
Journal: JAMA (1906)

The recent consolidation of the different forms of mania and of melancholia into the one disease called manic-depressive insanity is a notable achievement and at the same time furnishes one of the most important of the recent problems of psychiatry. The fusion of so widely differing symptom complexes into one type, and their presentation as a definite disease can only be justified by showing that the same pathologic process or, what is quite different, that the same cause underlies the manifestations in all cases. It is important to investigate and group the cases of so common a difficulty as the so-called manic depressive type, to find out whether the diagnostic criteria are justified, whether the prognosis is hopeless, as to permanent cure, as is implied in the definition ordinarily given of the disease and the treatment restricted to care and palliation, or whether some cases of the disease being curable,
Aggravation of post-ischemic liver injury by overexpression of A20, an NF-κB suppressor
Authors: Jiahua Yu, Hwa-Suk Lee, Sang-Myeong Lee, Hee-Chul Yu, Woo Sung Moon, Myoung Ja Chung, Jin-Woo Park, Byung-Hyun Park
Journal: Journal of Hepatology (2010)
Airway Fibroblasts Isolated from Mouse Model of Allergic Asthma Display Distinct Cellular and Phenotypic Characteristics as Compared to Normal Fibroblasts
Authors: A.I. Berro, H. Sugiura, X. Liu, F. Duan, S. Kawasaki, S. Togo, K. Kamio, X.Q. Wang, L. Mao, Y. Ahn, R.F. Ertl, T.B. Casale, S.I. Rennard
Journal: Journal of Allergy and Clinical Immunology (2007)
THE MILK SUPPLY OF BOSTON, AND THE BENEFIT TO BE DERIVED FROM THE SPAYING OF COWS.
Authors: LLOYD F. ABBOTT.
Journal: JAMA (1884)

The milk supply of Boston may be divided into three classes: first, that brought in on the cars, and commonly called railroad milk; second, that brought in wagons from the surrounding country, and called out-of-town milk; third, that from cows kept within the city limits. Each one of these may be divided into three classes: first, from the new milch cow; second, from the farrow cow, or one that has been milked for a year or more; third, from a springer, or one with calf. The nature of the new milk is very loosening; it is well known among farmers that the first milkings given to a calf three or four weeks will scour it to death. This milk changes as it increases in age, until at the end of a year the milk of a farrow cow becomes very astringent. This milk, if given to a calf a week