tbuckley/cabot-search huggingface dataset:
Deaths Attributable to Smallpox Vaccination, 1959 to 1966, and 1968
Authors: J. Michael Lane
Journal: JAMA (1970)

There were 68 deaths in the United States from complications of smallpox vaccination in the nine years 1959 to 1966, and 1968; 19 were associated with vaccinia necrosum, 36 were caused by postvaccinial encephalitis, 12 by eczema vaccinatum, and 1 by Stevens-Johnson syndrome. Of the 68 who died, 24 were infants, although only 12% of all primary vaccinations are given to this age group. All of the deaths from eczema vaccinatum were in children who were not vaccinated themselves, but acquired vaccinia from a sibling, playmate, or parent. This suggests that reduction of the number of deaths from eczema vaccinatum cannot be established by screening vaccinees alone. Reducing the number of primary vaccinations performed would lower the risks of acquiring eczema vaccinatum and postvaccinial encephalitis.
Humanized Anti-CD26 Monoclonal Antibody as a Treatment for Malignant Mesothelioma Tumors
Authors: Teruo Inamoto, Taketo Yamada, Kei Ohnuma, Shinichiro Kina, Nozomu Takahashi, Tadanori Yamochi, Sakiko Inamoto, Yoji Katsuoka, Osamu Hosono, Hirotoshi Tanaka, Nam H. Dang, Chikao Morimoto
Journal: Clinical Cancer Research (2007)

CD26 is a 110-kDa cell surface antigen with a role in tumor development. In this report, we show that CD26 is highly expressed on the cell surface of malignant mesothelioma and that a newly developed humanized anti-CD26 monoclonal antibody (mAb) has an inhibitory effect on malignant mesothelioma cells in both in vitro and in vivo experiments.Using immunohistochemistry, 12 patients' surgical specimens consisting of seven malignant mesothelioma, three reactive mesothelial cells, and two adenomatoid tumors were evaluated for expression of CD26. The effects of CD26 on malignant mesothelioma cells were assessed in the presence of transfection of CD26-expressing plasmid, humanized anti-CD26 mAb, or small interfering RNA against CD26. The in vivo growth inhibitory effect of humanized anti-CD26 mAb was assessed in human malignant mesothelioma cell mouse xenograft models.In surgical specimens, CD26 is highly expressed in malignant mesothelioma but not in benign mesothelial tissues. Depletion of CD26 by small interfering RNA results in the loss of adhesive property, suggesting that CD26 is a binding protein to the extracellular matrix. Moreover, our in vitro data indicate that humanized anti-CD26 mAb induces cell lysis of malignant mesothelioma cells via antibody-dependent cell-mediated cytotoxicity in addition to its direct anti-tumor effect via p27(kip1) accumulation. In vivo experiments with mouse xenograft models involving human malignant mesothelioma cells show that humanized anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival.Our data strongly suggest that humanized anti-CD26 mAb treatment may have potential clinical use as a novel cancer therapeutic agent in CD26-positive malignant mesothelioma.
Real-time Dose Adjustment of Cyclophosphamide in a Preparative Regimen for Hematopoietic Cell Transplant: A Bayesian Pharmacokinetic Approach
Authors: David H. Salinger, Jeannine S. McCune, Aaron G. Ren, Danny D. Shen, John T. Slattery, Brian Phillips, George B. McDonald, Paolo Vicini
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Dose-related toxicity of cyclophosphamide may be reduced and therapeutic efficacy may be improved by pharmacokinetic sampling and dose adjustment to achieve a target area under the curve (AUC) for two of its metabolites, hydroxycyclophosphamide (HCY) and carboxyethylphosphoramide mustard (CEPM). To facilitate real-time dose adjustment, we developed open-source code within the statistical software R that incorporates individual data into a population pharmacokinetic model. Experimental Design: Dosage prediction performance was compared to that obtained with nonlinear mixed-effects modeling using NONMEM in 20 cancer patients receiving cyclophosphamide. Bayesian estimation of individual pharmacokinetic parameters was accomplished from limited (i.e., five samples over 0-16 hours) sampling of plasma HCY and CEPM after the initial cyclophosphamide dose. Conditional on individual pharmacokinetics, simulations of the AUC of both HCY and CEPM were provided for a range of second doses (i.e., 0-100 mg/kg cyclophosphamide). Results: The results compared favorably with NONMEM and returned accurate predictions for AUCs of HCY and CEPM with comparable mean absolute prediction error and root mean square prediction error. With our method, the mean absolute prediction error and root mean square prediction error of AUC CEPM were 11.0% and 12.8% and AUC HCY were 31.7% and 44.8%, respectively. Conclusions: We developed dose adjustment software that potentially can be used to adjust cyclophosphamide dosing in a clinical setting, thus expanding the opportunity for pharmacokinetic individualization of cyclophosphamide. The software is simple to use (requiring no programming experience), reads individual patient data directly from an Excel spreadsheet, and runs in less than 5 minutes on a desktop PC.
Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model
Authors: Wenting Zheng, Zhihong Wang, Lijie Song, Qiang Zhao, Jun Zhang, Dong Li, Shufang Wang, Jihong Han, Xi-Long Zheng, Zhimou Yang, Deling Kong
Journal: Biomaterials (2012)
Urinary Incontinence in French Women: Prevalence, Risk Factors, and Impact on Quality of Life
Authors: Andrea Lasserre, Camille Pelat, Violaine Guéroult, Thomas Hanslik, Emmanuel Chartier-Kastler, Thierry Blanchon, Calin Ciofu, Emmanuel D. Montefiore, Fabián P. Alvarez, Juliette Bloch
Journal: European Urology (2009)
Mapping of the nu gene using congenic nude strains and in situ hybridization.
Authors: Y Takahashi, A Shimizu, T Sakai, Y Endo, N Osawa, H Shisa, T Honjo
Journal: The Journal of Experimental Medicine (1992)

The chromosomal location of the nu gene, which is responsible for hairlessness and athymus, was determined using six DNA markers (interleukin 3 [Il-3], Myhs, Acrb, Evi-2, Mpo, and Hox-2) on mouse chromosome 11. We constructed the high-resolution physical mapping of the six DNA markers on chromosome 11 by in situ hybridization using fluorescence-labeled cosmid probes. The results indicate the order of centromere-(41cM)-Il-3-(3cM)-Myhs- (4cM)-Acrb-(6cM)-Evi-2-(3cM)-Mpo-(5cM)- Hox-2. We have used congenic nude strains and examined which of the six DNA markers were derived from the original nude mouse. We found the Evi-2 locus is linked to the nu gene in all the informative, independent congenic nude strains. From these data, we could estimate the location of the nu gene, not only genetically but also physically within a region that spans approximately 17 megabases (9 cM) between the Acrb and Mpo genes.
Gene Expression Profiles of Primary Breast Carcinomas from Patients at High Risk for Local Recurrence after Breast-Conserving Therapy
Authors: Bas Kreike, Hans Halfwerk, Petra Kristel, Annuska Glas, Hans Peterse, Harry Bartelink, Marc J. van de Vijver
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Several risk factors for local recurrence of breast cancer after breast-conserving therapy (BCT) have been identified. The identification of additional risk factors would be very useful in guiding optimal therapy and also in improving understanding of the mechanisms underlying local recurrence. We used cDNA microarray analysis to identify gene expression profiles associated with local recurrence. Experimental Design: Using 18K cDNA microarrays, gene expression profiles were obtained from 50 patients who underwent BCT. Of these 50 patients, 19 developed a local recurrence; the remaining 31 patients were selected as controls as they were free of local recurrence at least 11 years after treatment. For 9 of 19 patients, the local recurrence was also available for gene expression profiling. Unsupervised and supervised methods of classification were used to separate patients in groups corresponding to disease outcome and to study the overall gene expression pattern of primary tumors and their recurrences. Results: Hierarchical clustering of patients did not show any grouping reflecting local recurrence status. Supervised analysis revealed no significant set of genes that was able to distinguish recurring tumors from nonrecurring tumors. Paired-data analysis of primary tumors and local recurrences showed a remarkable similarity in gene expression profile between primary tumors and their recurrences. Conclusions: No significant differences in gene expression between primary breast cancer tumors in patients with or without local recurrence after BCT were identified. Furthermore, analyses of primary tumors and local recurrences show a preservation of the overall gene expression pattern in the local recurrence, even after radiotherapy.
Hemodynamic response to pharmacological treatment of portal hypertension and long-term prognosis of cirrhosis
Authors: J Abraldes
Journal: Hepatology (2003)

In cirrhotic patients under pharmacologic treatment for portal hypertension, a reduction in hepatic venous pressure gradient (HVPG) of ≥20% of baseline or to ≤12 mm Hg markedly reduces the risk of variceal rebleeding. This study was aimed at evaluating whether these hemodynamic targets also prevent other complications of portal hypertension and improve long-term survival. One hundred five cirrhotic patients included in prospective trials for the prevention of variceal rebleeding were studied. Seventy-three of the patients had 2 separate HVPG measurements, at baseline and under pharmacologic therapy with propranolol ± isosorbide mononitrate. Patients were followed for up to 8 years. Survival and risk of developing portal hypertension-related complications were compared between responders and nonresponders. Twenty-eight patients showed a reduction of HVPG ≥20% of baseline or to ≤12 mm Hg (responders), and 45 patients were nonresponders. Nonresponders had a significantly greater risk of developing variceal rebleeding (P = .013), ascites (P = .025), spontaneous bacterial peritonitis (P = .003), hepatorenal syndrome (P = .026), and hepatic encephalopathy (P = .024) than responders. Eight-year cumulative probability of survival was significantly lower in nonresponders than in responders (52% vs. 95%, respectively, P = .003). At multivariate analysis, being a nonresponder was independently associated with the risk of developing rebleeding, ascites, spontaneous bacterial peritonitis, and lower survival. In conclusion, in cirrhotic patients receiving pharmacologic treatment for prevention of variceal rebleeding, a decrease in HVPG ≥20% or to ≤12 mm Hg is associated with a marked reduction in the long-term risk of developing complications of portal hypertension and with improved survival. (Hepatology 2003;37:902-908.)
Nomenclature of broncho-pulmonary anatomy: 60 years later
Authors: Wim Vos, Sergiy Volkovych, Cedric Van Holsbeke, Bart Veeckmans, Jan De Backer, Wilfried De Backer
Journal: European Respiratory Journal (2014)

Rationale 

The broncho-pulmonary (BP) anatomy has been extensively described in the '30-'50 of last century. In 1950 an article in Thorax [(1950), 5, 222] appeared summarizing an international effort resulting in a general accepted nomenclature of the BP anatomy. Although the article mentions the possibility of anatomic variations on a segmental level, this area has not been studied as of today. This study aims to investigate the occurrence of anatomical variations in a large population.

Methods 

100 spirometry controlled CT scans at TLC were analyzed retrospectively. Airway trees and centerlines were semi-automatically generated using Mimics 15.0 (Materialise, Belgium). All centerline labels were cross checked by the same 2 observers until mutual agreement was obtained. Anatomic variations were labelled in accordance to Ikeda (Netter 1979, see figure).

![Figure][1] 



Results 

9 anatomical variations on the accepted 18 segment model are observed in 68% of the patients. 4 of these segments are commonly found (yellow in figure) and 5 segments are rare (red). Details are given in the table.

View this table:



Conclusions 

As non-invasive retrospective CT analysis demonstrated, BP anatomy variations are not uncommon. It might be of interest to undertake an epidemiologic study to investigate the extent of anatomic variations in the BP anatomy.

 [1]: pending:yes
Helicobacter pylori: bridging the credibility gap.
Authors: A W McKinlay, R Upadhyay, C G Gemmell, R I Russell
Journal: Gut (1990)

In summary, therefore, there are interesting associations between H pylori, duodenal ulcer, and non-ulcer dyspepsia. In type B gastritis there may be enough evidence to suggest a causal role. The relation between gastritis and upper gastrointestinal symptomatology, however, remains contentious. The relation between H pylori and acid secretion may be more intimate than was previously thought. 9Pylorites9 must temper their enthusiasm and provide hard data; 9Schwartzians9 must broaden their horizons.
Human Dendritic Cells Activated by TSLP and CD40L Induce Proallergic Cytotoxic T Cells
Authors: Michel Gilliet, Vassili Soumelis, Norihiko Watanabe, Shino Hanabuchi, Svetlana Antonenko, Rene de Waal-Malefyt, Yong-Jun Liu
Journal: The Journal of Experimental Medicine (2003)

Human thymic stromal lymphopoietin (TSLP) is a novel epithelial cell-derived cytokine, which induces dendritic cell (DC)-mediated CD4+ T cell responses with a proallergic phenotype. Although the participation of CD8+ T cells in allergic inflammation is well documented, their functional properties as well as the pathways leading to their generation remain poorly understood. Here, we show that TSLP-activated CD11c+ DCs potently activate and expand naive CD8+ T cells, and induce their differentiation into interleukin (IL)-5 and IL-13-producing effectors exhibiting poor cytolytic activity. Additional CD40L triggering of TSLP-activated DCs induced CD8+ T cells with potent cytolytic activity, producing large amounts of interferon (IFN)-gamma, while retaining their capacity to produce IL-5 and IL-13. These data further support the role of TSLP as initial trigger of allergic T cell responses and suggest that CD40L-expressing cells may act in combination with TSLP to amplify and sustain pro-allergic responses and cause tissue damage by promoting the generation of IFN-gamma-producing cytotoxic effectors.
Intracellular calcium transient of working human myocardium of seven patients transplanted for congestive heart failure.
Authors: C F Vahl, A Bonz, T Timek, S Hagl
Journal: Circulation Research (1994)

The afterload dependence of the intracellular calcium transient in isolated working human myocardium was analyzed in both donor and recipient hearts of seven patients undergoing transplantation because of dilated cardiomyopathy. The intracellular calcium transient (recorded by the fura 2 ratio method), force development, and muscle shortening were simultaneously recorded in small (0.6 x 4.0-mm) electrically driven (60 beats per minute) trabeculas contracting at constant preload against varying afterloads. When the fibers contracted under isometric conditions, the intracellular calcium transients of normal and failing myocardium were similar. However, in dilated cardiomyopathy, stepwise afterload reduction and the concomitant increase in shortening amplitudes were associated with extraordinary alterations in the shape of the calcium transients; the amplitude rose, the time to peak was delayed, and at minimal afterloads, a long-lasting plateau was observed, and the diastolic decay was retarded. The calcium-time integral during shortening against passive resting force was 124 +/- 5% of the isometric control in normal myocardium and 172 +/- 12% in end-stage heart failure (P < .0001). We conclude that adequate interpretation of intracellular calcium transients requires simultaneous recordings of force and shortening. The extraordinary afterload dependence of the calcium transient in end-stage heart failure may be attributed to increased dissociation of calcium from the contractile proteins, a reduced calcium reuptake rate of the sarcoplasmic reticulum, or an increased calcium inflow due to altered permeabilities of the calcium channels during shortening. A potential role of mechanosensitive calcium channels has to be considered.
A Double-Negative Feedback Loop between ZEB1-SIP1 and the microRNA-200 Family Regulates Epithelial-Mesenchymal Transition
Authors: Cameron P. Bracken, Philip A. Gregory, Natasha Kolesnikoff, Andrew G. Bert, Jun Wang, M. Frances Shannon, Gregory J. Goodall
Journal: Cancer Research (2008)

Abstract Epithelial to mesenchymal transition occurs during embryologic development to allow tissue remodeling and is proposed to be a key step in the metastasis of epithelial-derived tumors. The miR-200 family of microRNAs plays a major role in specifying the epithelial phenotype by preventing expression of the transcription repressors, ZEB1/δEF1 and SIP1/ZEB2. We show here that miR-200a, miR-200b, and the related miR-429 are all encoded on a 7.5-kb polycistronic primary miRNA (pri-miR) transcript. We show that the promoter for the pri-miR is located within a 300-bp segment located 4 kb upstream of miR-200b. This promoter region is sufficient to confer expression in epithelial cells and is repressed in mesenchymal cells by ZEB1 and SIP1 through their binding to a conserved pair of ZEB-type E-box elements located proximal to the transcription start site. These findings establish a double-negative feedback loop controlling ZEB1-SIP1 and miR-200 family expression that regulates cellular phenotype and has direct relevance to the role of these factors in tumor progression. [Cancer Res 2008;68(19):7846–54]
Book: Opium and the People: Opiate Use and Drug Control Policy in Nineteenth Century England
Authors: M. Plant
Journal: BMJ (1999)

Virginia Berridge Free Association Books, £16.95, pp 370 ISBN 1 85343 413 2 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img>![Graphic][4]</img> Reading the revised edition of this acclaimed work is like renewing an acquaintance with an old friend. The 1981 book, though mainly written by Virginia Berridge, also included a section by Griffith Edwards. The new edition is solely the work of Virginia Berridge, a distinguished historian, who has produced a truly wonderful text. This provides the definitive overview of the widespread use of opium in Britain during the 19th and early … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif [4]: /embed/inline-graphic-4.gif
T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis.
Authors: A L Lazaar, S M Albelda, J M Pilewski, B Brennan, E Puré, R A Panettieri
Journal: The Journal of Experimental Medicine (1994)

Asthma is a disease of airway inflammation and hyperreactivity that is associated with a lymphocytic infiltrate in the bronchial submucosa. The interactions between infiltrating T lymphocytes with cellular and extracellular matrix components of the airway and the consequences of these interactions have not been defined. We demonstrate the constitutive expression of CD44 on human airway smooth muscle (ASM) cells in culture as well as in human bronchial tissue transplanted into severe combined immunodeficient mice. In contrast, basal levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression are minimal but are induced on ASM by inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha). Activated, but not resting T cells, adhere to cultured ASM; stimulation of the ASM with TNF-alpha enhanced this adhesion. Adhesion was partially blocked by monoclonal antibodies (mAb) specific for lymphocyte function-associated antigen 1 (LFA-1) and very late antigen 4 (VLA-4) on T cells and ICAM-1 and VCAM-1 on ASM cells. The observed integrin-independent adhesion was mediated by CD44/hyaluronate interactions as it was inhibited by anti-CD44 mAb 5F12 and by hyaluronidase. Furthermore, the adhesion of activated T lymphocytes induced DNA synthesis in growth-arrested ASM cells. Thus, the interaction between T cells and ASM may provide insight into the mechanisms that induce bronchial inflammation and possibly ASM cell hyperplasia seen in asthma.
GENETICS OF MANIC DEPRESSIVE ILLNESS
Authors: Dean F. MacKinnon, Kay Redfield Jamison, J. Raymond DePaulo
Journal: Annual Review of Neuroscience (1997)

▪ Abstract Manic depressive illness is a common and frequently debilitating familial psychiatric disorder. Efforts to understand the mechanisms of inheritance have been hindered by the complexity of the phenotype, which may range from benign mood swings to chronic psychosis, and by apparently nonmendelian modes of transmission. Early reports of linkage to chromosomal loci have fallen into doubt; however they have helped encourage the development of more sophisticated methods for analyzing complex phenotypes. Using such methods, linkage of manic depressive illness to loci on chromosome 18 has been reported and apparently replicated, and work is proceeding to identify genes associated with what is probably a genetically heterogeneous set of disorders. As molecular mechanisms of inheritance are elucidated, it will be important to consider the ethical implications of genetic testing in a clinically and genetically complex disorder such as manic depressive illness.
Outcomes of Patients With Esophageal Cancer Staged With [<sup>18</sup>F]Fluorodeoxyglucose Positron Emission Tomography (FDG-PET): Can Postchemoradiotherapy FDG-PET Predict the Utility of Resection?
Authors: Arta Monir Monjazeb, Greg Riedlinger, Mebea Aklilu, Kim R. Geisinger, Girish Mishra, Scott Isom, Paige Clark, Edward A. Levine, A. William Blackstock
Journal: Journal of Clinical Oncology (2010)

To determine whether [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) can delineate patients with esophageal cancer who may not benefit from esophagectomy after chemoradiotherapy.We reviewed records of 163 patients with histologically confirmed stage I to IVA esophageal cancer receiving chemoradiotherapy with or without resection with curative intent. All patients received surgical evaluation. Initial and postchemoradiotherapy FDG-PET scans and prognostic/treatment variables were analyzed. FDG-PET complete response (PET-CR) after chemoradiotherapy was defined as standardized uptake value ≤ 3.Eighty-eight patients received trimodality therapy and 75 received chemoradiotherapy. Surgery was deferred primarily due to medical inoperability or unresectable/metastatic disease after chemoradiotherapy. A total of 105 patients were evaluable for postchemoradiotherapy FDG-PET response. Thirty-one percent achieved a PET-CR. PET-CR predicted for improved outcomes for chemoradiotherapy (2-year overall survival, 71% v 11%, P < .01; 2-year freedom from local failure [LFF], 75% v 28%, P < .01), but not trimodality therapy. On multivariate analysis of patients treated with chemoradiotherapy, PET-CR is the strongest independent prognostic variable (survival hazard ratio [HR], 9.82, P < .01; LFF HR, 14.13, P < .01). PET-CR predicted for improved outcomes regardless of histology, although patients with adenocarcinoma achieved a PET-CR less often.Patients treated with trimodality therapy found no benefit with PET-CR, likely because FDG-PET residual disease was resected. Definitive chemoradiotherapy patients achieving PET-CR had excellent outcomes equivalent to trimodality therapy despite poorer baseline characteristics. Patients who achieve a PET-CR may not benefit from added resection given their excellent outcomes without resection. These results should be validated in a prospective trial of FDG-PET-directed therapy for esophageal cancer.