tbuckley/cabot-search huggingface dataset:
Feasibility Trial of Partial Breast Irradiation With Concurrent Dose-Dense Doxorubicin and Cyclophosphamide in Early-Stage Breast Cancer
Authors: Richard C. Zellars, Vered Stearns, Deborah Frassica, Fariba Asrari, Theodore Tsangaris, Lee Myers, Shirley DiPasquale, Julie R. Lange, Lisa K. Jacobs, Leisha A. Emens, Deborah K. Armstrong, John H. Fetting, Elizabeth Garrett-Mayer, Nancy E. Davidson, Antonio C. Wolff
Journal: Journal of Clinical Oncology (2009)

Anthracyclines and concurrent whole-breast irradiation result in prohibitive cutaneous toxicity. We hypothesized that anthracycline-based chemotherapy and concurrent partial breast irradiation (PBI) is safe and conducted a single-arm feasibility trial testing this hypothesis with dose-dense doxorubicin and cyclophosphamide (ddAC).Women with T1-2, N0-1 breast cancer with > or = 3 mm lumpectomy margins received PBI (40.5 Gy, 15 daily 2.7-Gy fractions) concurrently with the first two of four cycles of ddAC (60 and 600 mg/m2 of doxorubicin and cyclophosphamide, respectively, every 14 days with colony-stimulating support). Primary end points were local and systemic toxicity. Additional systemic therapy was given at the physician's discretion.Twenty-seven patients enrolled between November 2004 and January 2007, but two patients did not receive protocol therapy (one found with additional local disease and one withdrew consent). Twenty-five women completed all planned PBI. Four (16%) of 25 did not complete all ddAC (febrile neutropenia [FN], n = 2; diverticulitis and neutropenia, n = 1; and social/economic reasons, n = 1). Four among the remaining 21 who completed all ddAC had a cycle delayed (FN, n = 1; acute respiratory illness, n = 1; foot blisters, n = 1; perianal dermatitis, n = 1). There was no grade 3 to 4 anemia or thrombocytopenia. Grade 3 nonhematologic toxicities (none grade 4) occurred in 28% (seven of 25) of patients (nausea/vomiting, n = 3; stomatitis, n = 2; contralateral breast abscess, n = 1; fatigue, n = 1; and cough/bronchospasms, n = 1). The observed rate of > or = grade 2 skin toxicity was 0% (0 of 25; one-sided 95% CI, 0% to 11%).PBI with concurrent ddAC is feasible, and local/systemic toxicity is acceptable. Larger studies are warranted to assess long-term locoregional control and late toxicities.
Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers
Authors: Emilia Falkowska, Khoa M. Le, Alejandra Ramos, Katie J. Doores, Jeong Hyun Lee, Claudia Blattner, Alejandro Ramirez, Ronald Derking, Marit J. van Gils, Chi-Hui Liang, Ryan Mcbride, Benjamin von Bredow, Sachin S. Shivatare, Chung-Yi Wu, Po-Ying Chan-Hui, Yan Liu, Ten Feizi, Michael B. Zwick, Wayne C. Koff, Michael S. Seaman, Kristine Swiderek, John P. Moore, David Evans, James C. Paulson, Chi-Huey Wong, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, Pascal Poignard, Dennis R. Burton
Journal: Immunity (2014)
Polymorphisms of the 5' leader cistron of the human beta2-adrenergic receptor regulate receptor expression.
Authors: D W McGraw, S L Forbes, L A Kramer, S B Liggett
Journal: Journal of Clinical Investigation (1998)

Cellular expression of the beta2-adrenergic receptor (beta2AR) is controlled in part by a 19-amino acid peptide that regulates mRNA translation. This peptide is encoded by a short open reading frame, termed the 5' leader cistron (5'LC), which is 102 bp upstream of the beta2AR coding block. In 176 normal subjects we found a single nucleotide polymorphism resulting in either Arg (previously denoted wild-type) or Cys at position 19 of this peptide. Allele frequencies were 0.37 for Arg and 0.63 for Cys. To determine if these variants altered beta2AR expression, COS-7 cells were transfected with polymorphic constructs consisting of 1,989 bp encompassing the 5'LC and the beta2AR coding block exactly as found in the human gene. beta2AR density, as determined by [125I]CYP radioligand binding, was 72% higher in cells transfected with the 5'LC-Cys19 construct as compared with those transfected with the 5'LC-Arg19 construct and 110% higher when a cotransfection technique with a luciferase construct was used to control for transfection efficiency. Levels of the two mRNA transcripts were not different, confirming in vitro studies that the upstream peptide regulates receptor expression at the translational level. In human airway smooth muscle cells that natively express beta2AR, receptor expression was approximately twofold higher in those bearing the Cys versus the Arg polymorphism, confirming the phenotype in a relevant cell type. Linkage disequilibrium was observed between the 5'LC-Cys polymorphism and the beta2AR coding block polymorphisms Arg16 and Gln27 (P < 0.0001), although several different haplotypes were identified. Thus, beta2AR expression in the human population is controlled by a common polymorphism of this 5'LC, and may be responsible for interindividual variation in betaAR responsiveness.
Feasibility of the TNM‐based staging system of ocular adnexal extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma)
Authors: Sung‐Eun Lee, Ji‐Sun Paik, Won‐Kyung Cho, Byung‐Ock Choi, Sang‐Nam Lee, Seung‐Eun Jung, Kyung‐Sin Park, Chang‐Suk Kang, Sung‐Hoon Kim, Suk‐Woo Yang, Seok‐Goo Cho
Journal: American Journal of Hematology (2010)

The American Joint Committee on Cancer has proposed the tumor, node, metastasis (TNM) staging system to overcome the limitations of the Ann Arbor staging system for ocular adnexal lymphoma. We performed this study to evaluate the feasibility of the TNM staging system for ocular adnexal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (OAML). The data form 66 total eyes from 54 patients with biopsy-confirmed OAML according to World Health Organization classification were retrospectively analyzed. Using the TNM staging system, we reclassified all patients into two categories: (1) T1N0M0 stage group (n = 26), for patients with lymphoma involving only the conjunctiva; and (2) above T1N0M0 or bT1N0M0 stage group (n = 28), for patients with lymphoma extending to the orbit, eyelid, or adjacent structures, and/or bilateral OAML. After a 24-month median follow-up period for all patients, the T1N0M0 group revealed higher progression-free survival (PFS) than the above T1N0M0 or the bT1N0M0 group (P = 0.041). In a separate analysis of only 50 patients categorized as Ann Arbor stage IE, the T1N0M0 group demonstrated higher PFS (100%) than the above T1N0M0 or the bT1N0M0 group (84.7%; P = 0.067). Our data show that the poor prognostic group classified as Ann Arbor stage IE can be further distinguished by using the TNM staging system. Thus, further studies to develop treatment strategies for reducing relapse after treatment for OAML should use the TNM staging system.
Prolonged survival after portal decompression of patients with non-cirrhotic intrahepatic portal hypertension
Authors: R. Zeegen, A. G. Stansfeld, A. M. Dawson, A. H. Hunt
Journal: Gut (1970)

In a series of 251 good-risk patients undergoing portal decompression for intrahepatic portal hypertension, one fifth have been found not to have hepatic cirrhosis. Of these, 44 had only minor changes in hepatic architecture, and the clinical features and subsequent course have been compared and contrasted with a group of 201 cirrhotic patients who underwent portal decompression for similar indications. The degree of portal hypertension was comparable in both groups and it was not possible confidently to differentiate the condition from hepatic cirrhosis on either clinical or biochemical grounds in the individual case. The histological lesion was not progressive in the non-cirrhotic group and this was reflected in the far better survival of these patients. After five years 83% (30 of 36) of this group were alive compared with 43% (65 of 152) of the cirrhotic patients. After 10 years the cumulative survival was 77% (20 of 26) for those without cirrhosis, contrasted with 22% (19 of 87) for the cirrhotic patients.
Studies Probe Medication Use in Pregnancy
Authors: Bridget M. Kuehn
Journal: JAMA (2010)

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Clinical trials for tomorrow funded by the MRC
Authors: C. Warlow
Journal: BMJ (2003)

Future policy report raises several unanswered questions 

The Medical Research Council has an honourable tradition of supporting high quality randomised controlled trials. It funded one of the most celebrated early trials—of streptomycin for pulmonary tuberculosis, published in the BMJ in 1948.1 It has just published a commendably short 12 page report to determine its future policy and approach to randomised controlled trials2—so what does it say?

It is encouraging that the MRC intends to promote trials of so called complex interventions, where several components act both independently and interdependently. This is precisely where substantial methodological challenges are to be tackled—just what is the intervention, what outcomes are relevant, and how can the results be generalised to clinical practice? For example, the results of a trial of care in a stroke unit compared with care in a general medical ward must depend on the nature of the stroke unit and general medical ward being compared—their staffing, treatment policies, duration of admission, and so on. But although ring fenced funding for the development stage of such trials is welcome, the allocation of £250 000 ($405 000; €352 000) annually will hardly be enough to put trial proposals “on a more even footing with those involving drugs.” After all, the pharmaceutical companies spend millions to get …
Sensitivities of Colonies and Suspensions of Actinomyces Israelii to Penicillins, Tetracyclines, and Erythromycin
Authors: G. C. Blake
Journal: BMJ (1964)

MEDICAL JOHRNAL 14517 days from its onset.Twelve out of the 17 patients studied still had Eaton C.F. antibodies five months later.The incidence of Eaton pneumonia in 102 cases with cold agglutinins in titre > 32 was 26% and in 144 pneumonias without cold agglutinins 9%.Conversely, 68% of the Eaton pneumonias and 36% of non-Eaton pneumonias were cold- agglutinin-positive.In two control groups, comprising 484 blood donors and 118 surgical patients aged under 16 years, Eaton antibodies in titre > 8 were found in 5.4 and 32%.The corresponding figures for the same age-groups in the pneumonia series were 31 and 52%.These differences found between the pneumonia group and the control series were highly significant.None of the blood donors and only two of the surgical patients had an Eaton PPLO C.F. titre of 32.It is to be hoped that the results obtained by studying the Eaton PPLO C.F. antibodies in patients with pneumonia will stimulate the investigation of the role of PPLO in other human diseases.The C.F. technique provides a simple method.We wish to express our gratitude to Professor Thomas Anderson, Glasgow, for his criticism and valuable advice and for correcting the manuscript.We wish to thank Dr. Harri Nevanlinna, head of the Finnish Red Cross Blood Bank, for the blood donors' samples.We are also grateful to Dr
S2 Ethnic Variation in Inflammatory Profile in Tuberculosis
Authors: AR Martineau, AK Coussens, V Nikolayevskyy, PT Elkington, GH Bothamley, GE Packe, M Darmalingam, FA Drobniewski, RN Davidson, HJ Milburn, LV Baker, RD Barker, RJ Wilkinson, CJ Griffiths
Journal: Thorax (2012)

<h3>Introduction and objectives</h3> <i>Mycobacterium tuberculosis</i> (MTB) emerged as a pathogen in Africa and has co-evolved with humans following the migration to Europe and Asia some 70,000 years ago. Distinct phylogenetic lineages of MTB associate with hosts of particular genetic ancestry, both in their regions of origin and in distant cosmopolitan urban settings where human populations of different ancestry intermingle. These different strains induce distinct patterns of cytokine and chemokine secretion (‘inflammatory profiles’) in human macrophages. Circulating and antigen-stimulated inflammatory profiles might therefore be expected to vary significantly between tuberculosis patients of different ethnic origin. We therefore conducted a study to determine whether such variation exists. <h3>Methods</h3> We measured circulating and antigen-stimulated concentrations of 43 soluble inflammatory mediators and 14 haematological parameters in 45 patients of African ancestry and 83 patients of Eurasian ancestry receiving intensive-phase antimicrobial therapy for smear-positive pulmonary tuberculosis in London, UK. Host and bacillary genotypes were also determined. Statistical analyses were performed to compare inflammatory profiles in patients of African vs Eurasian ancestry; to investigate the influence of host and bacillary genotype on inflammatory profile; and to determine immunological correlates of speed of elimination of MTB from sputum. <h3>Results</h3> Tuberculosis patients of African vs Eurasian ancestry had similar clinical characteristics, but exhibited distinct inflammatory profiles. Patients of African ancestry had lower neutrophil counts, lower serum concentrations of CCL2, CCL11 and vitamin D binding protein (DBP), and lower antigen-stimulated CCL11 secretion than those of Eurasian ancestry, but higher serum CCL5 concentrations and higher antigen-stimulated interleukin 1 receptor antagonist and IL-12 secretion. These differences did not relate to MTB strain variation between groups, but they did associate with ethnic variation in host <i>DBP</i> genotype. Ethnic differences in inflammatory profile became more marked following initiation of antimicrobial therapy, and immunological correlates of speed of elimination of MTB from the sputum were distinct for patients of African vs. Eurasian ancestry. <h3>Conclusions</h3> Our study demonstrates a hitherto unappreciated degree of ethnic heterogeneity in inflammatory profile in tuberculosis patients. Candidate immunodiagnostics and immunological biomarkers of response to antimicrobial therapy should therefore be derived and validated in tuberculosis patients of different ethnic origin.
The early pattern of conjugated dienes in liver and lung after endotoxin exposure.
Authors: N C Clements, M P Habib
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

If lipid peroxidation (LP) contributes to organ dysfunction in sepsis rather than simply reflecting established injury, it should occur soon after the onset of the septic insult, and it may not progress uniformly in all organs. We assessed whether LP occurs within 90 min after onset of continuous intravenous endotoxin (E. coli 055:B5) infusion in rats, using second-derivative spectroscopy to semiquantitatively assess conjugated dienes (CD) in lung, liver, and plasma phospholipids. Measurements were also made after 90-min infusions with saline or 1 mM H2O2. Both the quantity and spectrophotometric patterns of CD differed between the three groups. Compared with saline controls, lung lipid CD increased after both H2O2 and endotoxin. Venous plasma CD were elevated only after H2O2, while arterial plasma and liver lipid CD were not different between the three groups. Exhaled ethane (an indicator of peroxidation of omega-3 fatty acids) did not differ between groups. Wet-to-dry lung weights were significantly increased after endotoxin compared with that after saline controls. Our results indicate that tissue-specific LP occurs within 90 min of endotoxin or H2O2 intravenous infusion.
Distinct recognition of antibodies to centromere proteins in primary Sjogren's syndrome compared with limited scleroderma
Authors: Allan C Gelber, Stanley R Pillemer, Bruce J Baum, Fredrick M Wigley, Laura K Hummers, Steven Morris, Antony Rosen, Livia A Casciola-Rosen
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> Anticentromere antibodies are characteristically observed in scleroderma but have recently been reported in other autoimmune rheumatic disorders, including Sjögren's syndrome. It is not known whether distinct centromere proteins (CENP) are targeted in primary Sjögren's syndrome (pSS) and scleroderma. <b>Objective:</b> To determine whether antibodies to CENP-B and CENP-C are present in these two disorders. <b>Methods:</b> Sera from 45 patients with pSS and 33 with limited scleroderma were studied. All patients met classification criteria for pSS and scleroderma, respectively. Sera were used to immunoprecipitate in vitro translated CENP-B and CENP-C. The proportions recognising CENP-B or CENP-C were compared. <b>Results:</b> 10 of 45 patients (22%) with pSS and 18 of 33 (55%) with scleroderma had antibodies recognising CENPs (p = 0.004). Seven of 10 (70%) CENP positive patients with pSS recognised CENP-C alone, compared with one of 18 (6%) CENP positive patients with scleroderma (odds ratio (OR) = 40 (95% confidence interval (CI), 3.5 to 450) (p = 0.003). In contrast, the majority (15 of 18 (83%)) of CENP positive scleroderma sera recognised both CENP-B and CENP-C, compared with none of 10 pSS sera (OR = 93 (95% CI, 4.4 to 1979) (p = 0.0001). <b>Conclusions:</b> The pattern of CENP recognition differs markedly in pSS and limited scleroderma. While patients with pSS predominantly recognise CENP-C alone, dual recognition of CENP-B and CENP-C is most frequent in scleroderma. These findings suggest that obtaining antibodies to specific centromere antigens is useful diagnostically, and imply that distinct mechanisms underlie the unique patterns of centromere autoreactivity in pSS and scleroderma.
Critical role of CD11b+ macrophages and VEGF in inflammatory lymphangiogenesis, antigen clearance, and inflammation resolution
Authors: Raghu P. Kataru, Keehoon Jung, Cholsoon Jang, Hanseul Yang, Reto A. Schwendener, Jung Eun Baik, Seung Hyun Han, Kari Alitalo, Gou Young Koh
Journal: Blood (2009)
The in vitro preconditioning of myoblasts to enhance subsequent survival in an in vivo tissue engineering chamber model
Authors: Daniel J. Tilkorn, E. Michele Davies, Effie Keramidaris, Aaron M. Dingle, Yi-Wen Gerrand, Caroline J. Taylor, Xiao Lian Han, Jason A. Palmer, Anthony J. Penington, Christina A. Mitchell, Wayne A. Morrison, Gregory J. Dusting, Geraldine M. Mitchell
Journal: Biomaterials (2012)
Psychoanalytic Concepts of Depression
Authors: Roy R. Grinker
Journal: JAMA (1961)

The author has done the psychiatric and psychoanalytic professions a great service in abstracting the main theoretical discussions containing psychoanalytic concepts of depression. He includes those writers who have contributed most to the theory on depression. They are Abraham, Freud, Rado, Gero, Melanie Klein, Bibring, Edith Jackson, and Mabel Blake Cohen. The abstracts of these writers are presented in understandable form as clear of technical language as is possible. Despite this attempt, psychoanalese often obscures what may possibly be cogent concepts, although this cannot be determined. It would have been pleasing to be able to report that this body of literature represented, in essence, a progress through the years of a Great Investigation. It does so in part. But perhaps even more does it represent a Great Debate, with the rhetorical rather than scientific implications of this word. Indeed at times it bears the stigma not of an exchange of
Cyclin D1 Expression in Breast Cancer Patients Receiving Adjuvant Tamoxifen-Based Therapy
Authors: Margaretha Rudas, Martina Lehnert, Anh Huynh, Raimund Jakesz, Christian Singer, Sigurd Lax, Walter Schippinger, Otto Dietze, Richard Greil, Wolfgang Stiglbauer, Werner Kwasny, Renate Grill, Michael Stierer, Michael F.X. Gnant, Martin Filipits
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The objective of our study was to determine the clinical relevance of cyclin D1 expression in hormone receptor–positive breast cancer patients who were treated with tamoxifen-based therapy. Experimental Design: We assessed expression of cyclin D1 in surgical specimens of breast carcinoma by means of immunohistochemistry. Patients had been enrolled in either Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathologic factors. Results: Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin D1 was associated with poor outcome in both cohorts. Overall survival was significantly shorter in patients with cyclin D1–positive tumors compared with patients with cyclin D1–negative tumors [adjusted hazard ratio (HR) for death (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03; adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P &amp;lt; 0.0001]. Relapse-free survival was also shorter in patients with cyclin D1–positive tumors than in patients with cyclin D1–negative tumors [adjusted HR for relapse (ABCSG Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005]. Conclusion: Cyclin D1 expression is an independent poor prognostic factor in women with early-stage, hormone receptor–positive breast cancer who received adjuvant tamoxifen-based therapy.
Cardiac Myosin Adenosinetriphosphatase Activity
Authors: ROBERT J. LUCHI, EVE Marie KRITCHER
Journal: Circulation Research (1966)

Cardiac myosin prepared by any one of a number of modifications of the basic Szent-Gyorgyi method and cardiac myosin prepared by the lithium chloride-ammonium sulfate technique differ in two important respects: 1) Szent-Gyorgyi-prepared myosin solutions are inhomogeneous by both chemical and immunologic criteria; 2) the ATPase activity of Szent-Gyorgyi-prepared myosin is low in comparison to lithium chloride-ammonium sulfate prepared cardiac myosin. Evidence is presented in this paper showing that the reduced ATPase activity of Szent-Gyorgyi-prepared cardiac myosin is the result of inhibition of the enzyme, possibly by a nucleotide contaminant, and a "diluting" effect of other nitrogen-containing contaminants of low specific activity. Many earlier studies indicate that cardiac and skeletal muscle myosin prepared by the Szent-Gyorgyi method differed strikingly in their ATPase activities. Comparison of lithium chloride-ammonium sulfate prepared cardiac and skeletal muscle myosin shows that skeletal muscle myosin has a slightly but significantly higher ATPase activity than canine cardiac myosin. A methodologic error was not excluded as the cause of this discrepancy. In a number of other characteristics, canine cardiac and skeletal muscle myosin ATPase activity was virtually identical.
Is there any arterial toxic effect after overlapping sirolimus-eluting stents?
Authors: Alexandre A. Abizaid, Juan S. Munoz, Ana C. Seixas, Andrea S. Abizaid, Fausto Feres, Luiz A. Mattos, Ibraim Pinto, Rodolfo Staico, Luiz F. Tanajura, Aurea J. Chaves, Marinella Centemero
Journal: Journal of the American College of Cardiology (2003)