tbuckley/cabot-search huggingface dataset:
Phase I Trial of the Trifunctional Anti-HER2 × Anti-CD3 Antibody Ertumaxomab in Metastatic Breast Cancer
Authors: Philipp Kiewe, Stephan Hasmüller, Steffen Kahlert, Maja Heinrigs, Brigitte Rack, Alexander Marmé, Agnieszka Korfel, Michael Jäger, Horst Lindhofer, Harald Sommer, Eckhard Thiel, Michael Untch
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Ertumaxomab is an intact bispecific antibody targeting HER2/neu and CD3 with selective binding to activatory Fcγ type I/III receptors, resulting in the formation of a tri-cell complex between tumor cells, T cells, and accessory cells. Patients with metastatic breast cancer were enrolled into a multicenter phase I dose-escalating trial. Experimental Design: Three ascending doses of ertumaxomab (10-200 μg) were administered i.v. on day 1, 7 ± 1, and 13 ± 1. Safety and tolerability were the primary objectives. Secondary objectives were antitumor activity and different immunologic variables. Results: Fifteen out of 17 enrolled patients completed the study. One hundred micrograms was identified as the maximal tolerable single dose. Most drug-related adverse events were mild and transient including fever (94%), rigors (47%), headache (35%), nausea (29%), vomiting (29%). Grades 3 and 4 (Common Toxicity Criteria) were lymphocytopenia (76%) and elevation of liver enzymes (47%). One patient (200 μg dose) developed severe hypotension and respiratory distress syndrome, another patient (150 μg dose) developed a systemic inflammatory response syndrome and acute renal failure. Aggravation of congestive heart failure was seen in one patient with preexisting ventricular dysfunction after administration of the third dose (200 μg). All adverse events were fully reversible. Antitumor response was seen in 5 out of 15 evaluable patients (one with a complete response, two with partial responses, two with stable disease) at dose levels of ≥100 μg. Measurements of cytokines (interleukin-6, interleukin-2, tumor necrosis factor-α, and IFN-γ) suggest a strong T helper cell type 1–associated immune response. The induction of human anti-mouse/anti-rat antibodies was detected in 5 out of 16 (31%) patients. Discussion: Treatment with triple infusions of ertumaxomab yields a strong immunologic response. Doses up to 100 μg can be safely infused with close monitoring of patients. The observed clinical responses are encouraging and indicate antitumor efficacy.
INDUCTION OF TOLERANCE TO HETEROLOGOUS PROTEINS AND THEIR CATABOLISM IN C57BL/6 MICE
Authors: Felix M. Dietrich, William O. Weigle
Journal: The Journal of Experimental Medicine (1963)

C57BL/6 mice were rendered tolerant to one or another of 13 soluble protein antigens. Tolerance was induced by a single injection of 20 mg protein within 24 hours after birth. The duration of the unresponsive state was measured and compared with the rates of catabolism of the antigens as determined in adult and new born mice. The data presented fail to show a correlation between the persistence of labeled protein antigen and the duration of tolerance. In several occasions, even an inverse relationship between duration of the unresponsive state and persistence was demonstrated. The results, therefore, strongly indicate that the duration of tolerance is not dependent on the rates of catabolism of the antigens. Several of the commercial protein preparations used in this study contained minor impurities to which the animals were generally not rendered tolerant. By means of diffusion in agar techniques, it was demonstrated that mice injected at birth with a tolerance-inducing dose of antigen would generally not reveal precipitating antibodies to this antigen after the tolerant state had been abolished. A speculative explanation was given in terms of quantitative or qualitative differences of antibodies found in such animals as compared to the immunized control mice. After the 3rd or 4th day of life, newborn mice catabolized I(131)-labeled heterologous proteins at the same rates as adult mice. The apparent slow elimination during the first days of life was, at least in part, the result of retention of nonprotein-bound I(131).
Survey of attitudes and knowledge about science in medical students in southeast Europe
Authors: Genc Burazeri, Marta Čivljak, Vesna Ilakovac, Slobodan Janković, Tanja Majica-Kovačević, Olesea Nedera, Enver Roshi, Valeriu Sava, Vladimir Šimunović, Ana Marušić, Matko Marušić
Journal: BMJ (2005)

For the countries of southeast Europe, joining the European Union would mean a fundamental reassessment of beliefs, attitudes, values, and structures developed during 50 years of communist regimes.1 This would include their healthcare systems and the training of their healthcare professionals. Medical schools in southeast Europe will need to restructure medical curriculums within the unified Europe.2 Medical students will have to learn modern evidence based medicine,3 for which they have not been prepared, mainly because of weak research output of their countries and inadequate education in research methods.4 To assess medical students' knowledge about research methods and communication and their attitudes towards research in medicine we used a specially constructed and validated questionnaire5 in medical schools in five post-communist countries.

In total 4307 students (66% response rate) answered a voluntary and anonymous questionnaire. The questionnaire contained a 45 item Likert-type scale developed to measure attitudes towards science, grouped in three subscales, and an eight item knowledge test of principles of scientific research.5 The study was performed simultaneously at all schools, …
Relationship Between Procedure Indications and Outcomes of Percutaneous Coronary Interventions by American College of Cardiology/American Heart Association Task Force Guidelines
Authors: H. Vernon Anderson, Richard E. Shaw, Ralph G. Brindis, Lloyd W. Klein, Charles R. McKay, Michael A. Kutcher, Ronald J. Krone, Michael J. Wolk, Sidney C. Smith, William S. Weintraub
Journal: Circulation (2005)

Background— An American College of Cardiology/American Heart Association (ACC/AHA) Task Force periodically revises and publishes guidelines with evidence-based recommendations for appropriate use of percutaneous coronary intervention (PCI). Some studies have suggested that closer adherence to guidelines can reduce variations in care, can improve quality, and may ultimately result in better outcomes, but this finding is incompletely understood. Guidelines themselves must change to be responsive to continuously evolving clinical practice. Our goal here was to investigate whether any relationship existed between the most recent ACC/AHA recommended indications for PCI and short term in-hospital outcomes. Methods and Results— We analyzed the ACC National Cardiovascular Data Registry for the period of January 1, 2001, through March 31, 2004. We excluded PCI procedures performed for acute myocardial infarction (ST-segment elevation myocardial infarction); all others were grouped by their indications according to the standard ACC/AHA scheme: Class I, evidence and/or agreement that PCI is useful and effective; Class IIa, conflicting evidence and/or divergent opinions, weight is in favor; Class IIb, usefulness/efficacy is less well established; and Class III, evidence and/or agreement that PCI is not useful or effective and may be harmful. Clinical success was defined as angiographic success (&lt;20% residual stenosis) at all lesions attempted without the adverse events of myocardial infarction, same-admission bypass surgery, or death. There were 412 617 PCI procedures included in the analysis. Frequency of indications was as follows: Class I, 64%; Class IIa, 21%; Class IIb, 7%; and Class III, 8%. Clinical success declined across the indications classes (92.8%, 91.7%, 89%, and 85.5%, respectively; P &lt;0.001), whereas adverse events increased. Conclusions— In this large survey of contemporary PCI practice, most procedures were performed for Class I indications. A significant relationship between evidence-based indications recommended by the ACC/AHA Task Force and in-hospital outcomes was noted.
ANTIGEN BINDING AND CAPPING BY LYMPHOCYTES OF GENETIC NONRESPONDER MICE
Authors: Edward K. Dunham, Emil R. Unanue, Baruj Benacerraf
Journal: The Journal of Experimental Medicine (1972)

Radioautographic study of the binding of GAT-(125)I to spleen cells of genetic responder and nonresponder mice demonstrates that among mice not injected with antigen all strains have approximately the same number of antigen-binding cells; after injection with antigen the number of antigen-binding cells increases in responders but not in nonresponders. Nonresponders are shown to make antibody after injection with GAT complexed with an immunogenic carrier, demonstrating the presence of potentially functional B cells in responders and nonresponders alike. When incubated in the warm, antigen-binding cells of both responders and nonresponders concentrate antigen at one pole of the cell, forming caps.
ULTRACENTRIFUGATION STUDIES ON THE ELEMENTARY BODIES OF VACCINE VIRUS
Authors: Edward G. Pickels, Joseph E. Smadel
Journal: The Journal of Experimental Medicine (1938)

Ultracentrifugal studies on the CL dermal strain of vaccine virus indicate the following characteristics of the elementary bodies:— 1. A stable suspension of Paschen bodies in a dilute buffer solution of pH 6.2 to 8 sediments with the formation of a characteristic primary boundary which consistently shows a spread of approximately 14 per cent. 2. The principal sedimentation boundary is accompanied frequently by one or several more rapidly moving boundaries which probably are produced by groups of agglutinated elementary bodies consisting of two or more particles. 3. Occasionally the principal boundary may exhibit an irregular or peculiar behavior, a fact which necessitates a careful selection of material and the performance of many experiments for accurate interpretation of results. 4. The sedimentation constant of the slowest moving particles forming the principal boundary is computed to be 49.1 x 10–11 cm./sec./dyne. On the basis of this sedimentation rate, the average diameter of the smallest virus particles in appreciable amounts is estimated at 236 mµ. If the boundary spread is due principally to slight differences in particle size, then the largest single elementary bodies are approximately 252 mµ in diameter.
Computed tomographic imaging of the airways: relationship to structure and function
Authors: P. A. de Jong, N. L. Müller, P. D. Paré, H. O. Coxson
Journal: European Respiratory Journal (2005)

Alterations in the structure of the airways, collectively termed airway remodelling, contribute to airflow obstruction in a variety of chronic lung diseases. While histology has provided valuable insights into the structure of airway wall remodelling, this technique is invasive and does not allow the longitudinal analysis of airway wall dimensions. Technical advances in computed tomography allow the assessment of airway wall dimensions, and are ideally suited for the noninvasive investigation of the pathogenesis of airway wall remodelling and the evaluation of new therapeutic interventions. The aim of this article is to review the use of computed tomography in the investigation of airway structure and function in health and disease.
NEUTRALIZATION OF EPIDEMIC INFLUENZA VIRUS
Authors: Frank L. Horsfall
Journal: The Journal of Experimental Medicine (1939)

A linear relationship exists between the logarithm of the quantity of epidemic influenza virus neutralized and the logarithm of the quantity of antiserum which is capable of achieving this result. This relationship is the same for the serum of a ferret convalescent from experimental influenza as for the serum of a rabbit immunized with the virus. By means of the linear relationship between virus and antiserum it is possible to determine a fixed, rather than a relative, value for the neutralizing capacity of a serum.
Semantic activation without conscious identification in dichotic listening, parafoveal vision, and visual masking: A survey and appraisal
Authors: Daniel Holender
Journal: Behavioral and Brain Sciences (1986)

Abstract When the stored representation of the meaning of a stimulus is accessed through the processing of a sensory input it is maintained in an activated state for a certain amount of time that allows for further processing. This semantic activation is generally accompanied by conscious identification, which can be demonstrated by the ability of a person to perform discriminations on the basis of the meaning of the stimulus. The idea that a sensory input can give rise to semantic activation without concomitant conscious identification was the central thesis of the controversial research in subliminal perception. Recently, new claims for the existence of such phenomena have arisen from studies in dichotic listening, parafoveal vision, and visual pattern masking. Because of the fundamental role played by these types of experiments in cognitive psychology, the new assertions have raised widespread interest. The purpose of this paper is to show that this enthusiasm may be premature. Analysis of the three new lines of evidence for semantic activation without conscious identification leads to the following conclusions. (1) Dichotic listening cannot provide the conditions needed to demonstrate the phenomenon. These conditions are better fulfilled in parafoveal vision and are realized ideally in pattern masking. (2) Evidence for the phenomenon is very scanty for parafoveal vision, but several tentative demonstrations have been reported for pattern masking. It can be shown, however, that none of these studies has included the requisite controls to ensure that semantic activation was not accompanied by conscious identification of the stimulus at the time of presentation. (3) On the basis of current evidence it is most likely that these stimuli were indeed consciously identified.
A patient with clinicopathologic features of small plaque parapsoriasis presenting later with plaque-stage mycosis fungoides: Report of a case and comparative retrospective study of 27 cases of “nonprogressive” small plaque parapsoriasis
Authors: Irena E. Belousova, Tomas Vanecek, Alexey V. Samtsov, Michal Michal, Dmitry V. Kazakov
Journal: Journal of the American Academy of Dermatology (2008)
Association Between Diagnosed Diabetes and Self-Reported Cancer Among U.S. Adults
Authors: Chaoyang Li, Lina S. Balluz, Earl S. Ford, Catherine A. Okoro, James Tsai, Guixiang Zhao
Journal: Diabetes Care (2011)

To assess the association between diagnosed diabetes and self-reported cancer among U.S. adults.We analyzed data for 397,783 adults who participated in the 2009 Behavioral Risk Factor Surveillance System and had valid data on diabetes and cancer.After adjustment for potential confounders, diabetic men had higher adjusted prevalence ratios for cancers of the prostate (1.1 [95% CI 1.0-1.3]), colon (1.3 [1.0-1.7]), pancreas (4.6 [1.8-11.7]), rectum (2.2 [1.0-4.7]), urinary bladder (1.7 [1.2-2.2]), and kidney (1.9 [1.2-3.0]) than nondiabetic men (all P < 0.05). Diabetic women had higher adjusted prevalence ratios for cancers of the breast (1.1 [1.0-1.3]) and endometrium (1.6 [1.2-2.0]), and leukemia (2.3 [1.3-4.2]) than nondiabetic women (all P < 0.05).Our results suggest that diabetic adults have higher prevalences of certain cancers than nondiabetic adults.
Immunogenotype Changes Prevail in Relapses of Young Children with <i>TEL-AML1</i>-Positive Acute Lymphoblastic Leukemia and Derive Mainly from Clonal Selection
Authors: E. Renate Panzer-Grümayer, Giovanni Cazzaniga, Vincent H.J. van der Velden, Laura del Giudice, Martina Peham, Georg Mann, Conny Eckert, Andre Schrauder, Giuseppe Germano, Jochen Harbott, Giuseppe Basso, Andrea Biondi, Jacques J.M. van Dongen, Helmut Gadner, Oskar A. Haas
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Variations of the immunogenotype and TEL deletions in children with TEL-AML1+ acute lymphoblastic leukemia support the hypothesis that relapses derive from a persistent TEL-AML1+ preleukemic/leukemic clone rather than a resistant leukemia. We aimed at elucidating the relationship between the immunogenotype patterns at diagnosis and relapse as well as their clinical and biological relevance. Patients and Methods: Immunoglobulin and T-cell receptor gene rearrangements were analyzed in 41 children with a TEL-AML1+ acute lymphoblastic leukemia and an early (up to 30 months after diagnosis; n = 12) or late (at 30 months or later; n = 29) disease recurrence by a standardized PCR approach. Results: In 68% of the patients (group I), we identified differences in the immunogenotype patterns, whereas no changes were observed in the remaining 32% (group II). The divergence resulted more often from clonal selection than clonal evolution and consisted predominantly of losses (0-6, median 5) and/or gains (0-4, median 1) of rearrangements. The frequency and number of clonal immunoglobulin/T-cell receptor rearrangements in group I was higher at diagnosis (2-13, median 5) than at relapse (2-7, median 4), whereas it was the lowest in group II (1-5, median 3). Although group I children were younger at diagnosis, there was no correlation between particular immunogenotype patterns and remission duration. Conclusion: These findings imply that the clonal heterogeneity in younger children most likely reflects an ongoing high recombinatorial activity in the preleukemic/leukemic cells, whereas the more uniform repertoire observed in older children mirrors end-stage rearrangement patterns of selected cell clones that evolved during the prolonged latency period.
Copy Number Variations in Schizophrenia: Critical Review and New Perspectives on Concepts of Genetics and Disease
Authors: Anne S. Bassett, Stephen W. Scherer, Linda M. Brzustowicz
Journal: American Journal of Psychiatry (2010)

Objective Structural variations of DNA, such as copy number variations (CNVs), are recognized to contribute both to normal genomic variability and to risk for human diseases. For example, schizophrenia has an established connection with 22q11.2 deletions. Recent genome-wide studies have provided initial evidence that CNVs at other loci may also be associated with schizophrenia. In this article, the authors provide a brief overview of CNVs, review recent findings related to schizophrenia, outline implications for clinical practice and diagnostic subtyping, and make recommendations for future reports on CNVs to improve interpretation of results. Method The review included genome-wide surveys of CNVs in schizophrenia that included one or more comparison groups, were published before 2009, and used newer methods. Six studies were identified. Results Despite some limitations, these initial genome-wide studies of CNVs provide replicated associations of schizophrenia with rare 1q21.1 and 15q13.3 deletions. Collectively, the results point to a more general mutational mechanism involving rare CNVs that elevate risk for schizophrenia, especially more developmental forms of the disease. Including 22q11.2 deletions, rare risk-associated CNVs appear to account for up to 2% of schizophrenia. Conclusions The more penetrant CNVs have direct implications for clinical practice and diagnostic subtyping. CNVs with lower penetrance promise to contribute to our genetic understanding of pathogenesis. The findings provide insight into a broader neuropsychiatric spectrum for schizophrenia than previously conceived and indicate new directions for genetic studies.
Host resistance directed selectively against H-2-deficient lymphoma variants. Analysis of the mechanism.
Authors: H G Ljunggren, K Kärre
Journal: The Journal of Experimental Medicine (1985)

Three independent variants with a profound reduction of cell surface H-2 have been selected from the C57BL/6 mouse-derived RBL-5 and EL-4 T lymphomas. After subcutaneous inoculation of low cell doses in syngeneic mice, the H-2- variants failed to grow out, whereas the H-2+ control lines showed progressive growth. No difference in growth rate or cloning efficiency was detectable in tissue culture. The in vivo difference in tumor outgrowth was analyzed in detail for one of the H-2-low lines. The outgrowth difference remained after the H-2-low variant and the control line had been injected subcutaneously in opposite flanks of the same mouse, and it was not dependent upon activity of mature T cells, since the same result was seen in athymic nude mice. The difference was partially sensitive to irradiation of the hosts. When mice were pretreated with anti-asialo GM1 antiserum, known to depress natural killer (NK) cell activity, the difference in outgrowth was abolished, and both the control line and the H-2- variant showed progressive growth in vivo. Experiments comparing the distribution and survival of isotope-prelabeled variant and wild type cells indicated that a rapid elimination of the former took place within 24 h after intravenous injection. These differences in tumor elimination were not seen in mice treated with anti-asialo GM1 antiserum. We conclude that the reduced tumorigenicity of sublines with impaired H-2 expression is largely, if not exclusively due to rapid elimination by NK cells. These findings may reflect an inverse, indirect relation between factors controlling H-2 expression and NK sensitivity. Another possible explanation is that major histocompatibility complex (MHC)-encoded gene products are directly involved in a regulatory signal in the NK cell system. According to this interpretation, immunological selectivity in the NK cell system would be achieved by the failure to recognize self-MHC, irrespective of the presence of foreign antigens, i.e. by detection of no-self rather than of nonself. This may also explain previous observations on H-2-linked hybrid resistance against lymphoid grafts and changes in H-2 phenotypes associated with tumor progression.
DNA Polymerase β Interacts with TRF2 and Induces Telomere Dysfunction in a Murine Mammary Cell Line
Authors: Poppy Fotiadou, Octavian Henegariu, Joann B. Sweasy
Journal: Cancer Research (2004)

DNA polymerase beta (Polbeta) is a DNA repair protein that functions in base excision repair and meiosis. The enzyme has deoxyribose phosphate lyase and polymerase activity, but it is error prone because it bears no proofreading activity. Errors in DNA repair can lead to the accumulation of mutations and consequently to tumorigenesis. Polbeta expression has been found to be higher in tumors, and deregulation of its expression has been found to induce chromosomal instability, a hallmark of tumorigenesis, but the underlying mechanisms are unclear. In the present study, we have investigated whether ectopic expression of Polbeta influences the stability of chromosomes in a murine mammary cell line. The results demonstrate a telomere dysfunction phenotype: an increased rate of telomere loss and chromosome fusion, suggesting that ectopic expression of Polbeta leads to telomere dysfunction. In addition, Polbeta interacts with TRF2, a telomeric DNA binding protein. Colocalization of the two proteins occurs at nontelomeric sites and appears to be influenced by the change in the status of the telomeric complex.