tbuckley/cabot-search huggingface dataset:
AN IDIOTYPIC CROSS-REACTION BETWEEN ALLOTYPE a3 AND ALLOTYPE a NEGATIVE RABBIT ANTIBODIES TO STREPTOCOCCAL CARBOHYDRATE
Authors: Thomas J. Kindt, David G. Klapper, Michael D. Waterfield
Journal: The Journal of Experimental Medicine (1973)

Two antibodies to Group C streptococcal carbohydrate isolated from an individual rabbit had similar relative binding affinities for a Group C immuno-adsorbent column. Their light chains were similar, if not identical, as were the constant regions of their heavy chains. Differences in the variable regions of the H chains of the two antibodies were detected by chemical analysis. The two antibodies had serologically identical idiotypic determinants although one antibody possessed the a3 allotype and the other had no detectable group a marker. The occurrence of such antibodies indicates the absence of obligatory associations between group a allotypes and idiotypic specificities, despite the fact that both determinants have antigenic components in the V(H) region of the H chain.
Targeting HER2 + breast cancer cells: Lysosomal accumulation of anti-HER2 antibodies is influenced by antibody binding site and conjugation to polymeric nanoparticles
Authors: Shawn C. Owen, Nish Patel, Jennifer Logie, Guohua Pan, Helena Persson, Jason Moffat, Sachdev S. Sidhu, Molly S. Shoichet
Journal: Journal of Controlled Release (2013)
Patent foramen ovale causing position-dependent shunting in a patient, when laying down her corset
Authors: J.C. Grutters, J.M. ten Berg, J. van der Zeijden, W. Jaarsma, J.M.P.G. Ernst, C.J.J. Westermann
Journal: European Respiratory Journal (2001)

A 75-;yr-old female presented with platypnoea and orthodeoxia, shortly after laying down an old and pinching corset. The injection of activated Haemaccel in the right cubital vene during transoesophageal echocardiography, in the upright position, revealed a direct blood flow from the superior caval vein at a patent foremen ovale, consequently opening it and causing a large right-to-left shunt which was calculated at 28.5%. In the supine position there was only a minimal opening of the patent foremen ovale with a calculated right-to-left shunt of 9.5%. The patent foremen ovale was successfully closed percutaneously with a CardioSEAL TM .
G-CSF for stem cell therapy in acute myocardial infarction: friend or foe?
Authors: W. Shim, A. Mehta, S. Y. Lim, G. Zhang, C. H. Lim, T. Chua, P. Wong
Journal: Cardiovascular Research (2010)

Stem cell-based therapy has emerged as a potential therapeutic option for patients with acute myocardial infarction. The ability of granulocyte colony-stimulating factor (G-CSF) to mobilize endogenous stem cells as well as to protect cardiomyocytes at risk via paracrine effects has attracted considerable attention. In the past decade, a number of clinical trials were carried out to study the efficacy of G-CSF in cardiac repair. These trials showed variable outcomes in terms of improved cardiac contractile function and suppressed left ventricular negative remodelling. Critical examinations of these results have raised doubts concerning the effectiveness of G-CSF in modulating functional recovery. However, these cumulative clinical experiences are helpful in the understanding of mechanisms and roles of signalling pathways in regulating homing and engraftment of bone marrow stem cells to the infarcted heart. In this review, we discuss some of the observations that may have influenced the clinical outcomes. Improving strategies that target the critical aspects of G-CSF-driven cardiac therapy may provide a better platform to augment clinical benefits in future trials.
Low PIAS3 Expression in Malignant Mesothelioma Is Associated with Increased STAT3 Activation and Poor Patient Survival
Authors: Snehal Dabir, Amy Kluge, Adam Kresak, Michael Yang, Pingfu Fu, Bernd Groner, Gary Wildey, Afshin Dowlati
Journal: Clinical Cancer Research (2014)

Deregulation of STAT3 activation is a hallmark of many cancer cells, and the underlying mechanisms are subject to intense investigation. We examined the extent of PIAS3 expression in mesothelioma cells and human tumor samples and determined the functional effects of PIAS3 expression on STAT3 signaling.We evaluated the expression of PIAS3 in mesothelioma tumors from patients and correlated the expression levels with the course of the disease. We also measured the effects of enhanced PIAS3 activity on STAT3 signaling, cellular growth, and viability in cultured mesothelioma cells.Gene expression databases revealed that mesotheliomas have the lowest levels of PIAS3 transcripts among solid tumors. PIAS3 expression in human mesothelioma tumors is significantly correlated with overall survival intervals (P = 0.058). The high expression of PIAS3 is predictive of a favorable prognosis and decreases the probability of death within one year after diagnosis by 44%. PIAS3 expression is functionally linked to STAT3 activation in mesothelioma cell lines. STAT3 downregulation with siRNA or enhanced expression of PIAS3 both inhibited mesothelioma cell growth and induced apoptosis. Mesothelioma cells are sensitive to curcumin and respond by the induction of PIAS3. Corroborative evidence has been obtained from STAT3 inhibition experiments. Exposure of the cells to a peptide derived from the PIAS3 protein that interferes with STAT3 function resulted in apoptosis induction and the inhibition of cell growth.These results suggest that PIAS3 protein expression impacts survival in patients with mesothelioma and that PIAS3 activation could become a therapeutic strategy. Clin Cancer Res; 20(19); 5124-32. ©2014 AACR.
Human histocompatibility determinants and virus antigens: effect of measles virus infection on HLA expression.
Authors: M V Haspel, M A Pellegrino, P W Lampert, M B Oldstone
Journal: The Journal of Experimental Medicine (1977)

Histocompatibility antigens on the surface of human lymphoblastoid cells were quantified by a microadsorption technique. During the course of measles virus infection, no quantitative or qualitations in surface HLA antigens were observed. In contrast, infection with poliovirus type 1 or vesicular stomatitis virus, or treatment with puromycin (50 microgram/ml) resulted in a significant decrease in surface HLA. These experiments suggest that an inhibition of host protein synthesis rather than the insertion of virus-specificied antigens into the membrane results in a net decrease in amounts of this cell surface antigen. The HLA antigens also appear to be both functionally and structurally distinct from measles virus surface antigens. Pretreatment of cells with HLA-directed antibody did not prevent the infection of these cells by measles virus, thus HLA antigens appear unrelated to the measles virus receptor site on the plasma membrane. Electron microscopic studies revealed that measles virus maturation occurs at membrane sites devoid of demonstrable HLA. Furthermore, HLA antigens could not be detected on the surfaces of mature infectious virions.
Phase III Randomized Trial of <i>Calendula Officinalis</i> Compared With Trolamine for the Prevention of Acute Dermatitis During Irradiation for Breast Cancer
Authors: P. Pommier, F. Gomez, M.P. Sunyach, A. D'Hombres, C. Carrie, X. Montbarbon
Journal: Journal of Clinical Oncology (2004)

Purpose The effectiveness of nonsteroid topical agents for the prevention of acute dermatitis during adjuvant radiotherapy for breast carcinoma has not been demonstrated. The goal of this study was to compare the effectiveness of calendula (Pommade au Calendula par Digestion; Boiron Ltd, Levallois-Perret, France) with that of trolamine (Biafine; Genmedix Ltd, France), which is considered in many institutions to be the reference topical agent. Patients and Methods Between July 1999 and June 2001, 254 patients who had been operated on for breast cancer and who were to receive postoperative radiation therapy were randomly allocated to application of either trolamine (128 patients) or calendula (126 patients) on the irradiated fields after each session. The primary end point was the occurrence of acute dermatitis of grade 2 or higher. Prognostic factors, including treatment modalities and patient characteristics, were also investigated. Secondary end points were the occurrence of pain, the quantity of topical agent used, and patient satisfaction. Results The occurrence of acute dermatitis of grade 2 or higher was significantly lower (41% v 63%; P &lt; .001) with the use of calendula than with trolamine. Moreover, patients receiving calendula had less frequent interruption of radiotherapy and significantly reduced radiation-induced pain. Calendula was considered to be more difficult to apply, but self-assessed satisfaction was greater. Body mass index and adjuvant chemotherapy before radiotherapy after lumpectomy were significant prognostic factors for acute dermatitis. Conclusion Calendula is highly effective for the prevention of acute dermatitis of grade 2 or higher and should be proposed for patients undergoing postoperative irradiation for breast cancer.
Myeloperoxidase Serum Levels Predict Risk in Patients With Acute Coronary Syndromes
Authors: Stephan Baldus, Christopher Heeschen, Thomas Meinertz, Andreas M. Zeiher, Jason P. Eiserich, Thomas Münzel, Maarten L. Simoons, Christian W. Hamm
Journal: Circulation (2003)

Background— Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS). Myeloperoxidase (MPO), a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent proinflammatory properties and may contribute directly to tissue injury. However, whether MPO also provides prognostic information in patients with ACS remains unknown. Methods and Results— MPO serum levels were assessed in 1090 patients with ACS. We recorded death and myocardial infarctions during 6 months of follow-up. MPO levels did not correlate with troponin T, soluble CD40 ligand, or C-reactive protein levels or with ST-segment changes. However, patients with elevated MPO levels (&gt;350 μg/L; 31.3%) experienced a markedly increased cardiac risk (adjusted hazard ratio [HR] 2.25 [1.32 to 3.82]; P =0.003). In particular, MPO serum levels identified patients at risk who had troponin T levels below 0.01 μg/L (adjusted HR 7.48 [95% CI 1.98 to 28.29]; P =0.001). In a multivariate model that included other biochemical markers, troponin T (HR 1.99; P =0.023), C-reactive protein (1.25; P =0.044), vascular endothelial growth factor (HR 1.87; P =0.041), soluble CD40 ligand (HR 2.78; P &lt;0.001), and MPO (HR 2.11; P =0.008) were all independent predictors of the patient’s 6-month outcome. Conclusions— In patients with ACS, MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers. Given its proinflammatory properties, MPO may serve as both a marker and mediator of vascular inflammation and further points toward the significance of PMN activation in the pathophysiology of ACS.
Detoxifying enzyme genotypes and susceptibility to cutaneous malignancy
Authors: J.T. Lear, A.G. Smith, R.C. Strange, A.A. Fryer
Journal: British Journal of Dermatology (2000)

While ultraviolet (UV) exposure is thought to be a major risk factor for basal cell carcinoma (BCC) and squamous cell carcinoma, more recent research has focused on genetic factors predisposing to these cancers. UV constitutes an oxidative stress with generation of free radicals, leading to lipid and DNA damage and gene mutation. It could therefore be hypothesized that individual ability to deal with these products may be important in cutaneous carcinogenesis. It is clear from recent studies that polymorphisms in detoxifying enzyme genes are important in determining susceptibility to skin cancer. The magnitude of effect in BCC is similar to that seen with many other previously described risk factors. However, uncertainties exist regarding the phenotypic consequences of some of these polymorphisms and relevant substrates. This review describes the influence of polymorphisms in detoxifying enzymes in determining susceptibility to skin cancer (in particular to BCC) and give a brief overview of the biochemistry of the detoxification process.
Incidence of Initial Local Therapy Among Men With Lower-Risk Prostate Cancer in the United States
Authors: David C. Miller, Stephen B. Gruber, Brent K. Hollenbeck, James E. Montie, John T. Wei
Journal: JNCI Journal of the National Cancer Institute (2006)

The frequently indolent nature of early-stage prostate cancer in older men and in men with low- or moderate-grade tumors and the demonstration that the survival benefits of radical prostatectomy are primarily among men younger than 65 years have led to concerns about prostate cancer overtreatment.Using data from 13 Surveillance, Epidemiology, and End Results registries, we performed a retrospective cohort study of 71,602 men who were diagnosed with localized or regional prostate cancer between 2000 and 2002. We quantified the incidence of initial curative therapy (i.e., surgery or radiation therapy) among men with lower-risk cancers as defined by their limited likelihood of either dying from expectantly managed prostate cancer or achieving a survival benefit from local therapy. Stratified analyses and multinomial logistic regression models were used to quantify the absolute and relative rates of curative therapy among men in various age-grade strata. All statistical tests were two-sided.We identified 24,405 men with lower-risk prostate cancers and complete data for the first course of treatment. Initial curative therapy was undertaken in 13,537 of these men (55%); 81% of treated men received radiation therapy. The likelihood of curative therapy, relative to expectant management, varied statistically significantly among lower-risk age-grade strata (all P<.05). Assuming that initial expectant management is appropriate for all lower-risk cancers, 2564 men (10%) in this population-based sample were overtreated with radical prostatectomy and 10,973 (45%) with radiation therapy.These data quantify a target population for whom greater use of expectant approaches may reduce overtreatment and improve the quality of localized prostate cancer care.
Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion
Authors: Alan List, Gordon Dewald, John Bennett, Aristotle Giagounidis, Azra Raza, Eric Feldman, Bayard Powell, Peter Greenberg, Deborah Thomas, Richard Stone, Craig Reeder, Kenton Wride, John Patin, Michele Schmidt, Jerome Zeldis, Robert Knight
Journal: New England Journal of Medicine (2006)

Severe, often refractory anemia is characteristic of the myelodysplastic syndrome associated with chromosome 5q31 deletion. We investigated whether lenalidomide (CC5013) could reduce the transfusion requirement and suppress the abnormal 5q31- clone in patients with this disorder.One hundred forty-eight patients received 10 mg of lenalidomide for 21 days every 4 weeks or daily. Hematologic, bone marrow, and cytogenetic changes were assessed after 24 weeks of treatment by an intention-to-treat analysis.Among the 148 patients, 112 had a reduced need for transfusions (76%; 95% confidence interval [CI], 68 to 82) and 99 patients (67%; 95% CI, 59 to 74) no longer required transfusions, regardless of the karyotype complexity. The response to lenalidomide was rapid (median time to response, 4.6 weeks; range, 1 to 49) and sustained; the median duration of transfusion independence had not been reached after a median of 104 weeks of follow-up. The maximum hemoglobin concentration reached a median of 13.4 g per deciliter (range, 9.2 to 18.6), with a corresponding median rise of 5.4 g per deciliter (range, 1.1 to 11.4), as compared with the baseline nadir value before transfusion. Among 85 patients who could be evaluated, 62 had cytogenetic improvement, and 38 of the 62 had a complete cytogenetic remission. There was complete resolution of cytologic abnormalities in 38 of 106 patients whose serial bone marrow samples could be evaluated. Moderate-to-severe neutropenia (in 55% of patients) and thrombocytopenia (in 44%) were the most common reasons for interrupting treatment or adjusting the dose of lenalidomide.Lenalidomide can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients who have the myelodysplastic syndrome with the 5q31 deletion. (ClinicalTrials.gov number, NCT00065156 [ClinicalTrials.gov].).
Effect of Computer-Based Learning on Diabetes Knowledge and Control
Authors: P H Wise, D C Dowlatshahi, S Farrant, S Fromson, K A Meadows
Journal: Diabetes Care (1986)

Two interactive computer-based systems have been evaluated: a teaching program with text and animated graphics and a multiple-choice knowledge-assessment program (KAP) with optional prescriptive feedback. One hundred seventy-four routine-attending insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients were allocated to active and control groups to determine the effect of these programs on knowledge and control after a 4- to 6-mo follow-up period. Interactive computer teaching (ICT) resulted in a significant knowledge increment in both IDDM and NIDDM patients (P &amp;lt; .05), together with a mean fall of 0.8 and 0.7%, respectively, in HbA1c (P &amp;lt; .05 and P &amp;gt; .1), but no changes were observed in respective control groups. The KAP with feedback also produced a significant knowledge increment in both IDDM and NIDDM patients (P &amp;lt; .05), of similar magnitude to the ICT program, and a mean fall in HbA1c of 1.2 and 1.3%, respectively (P &amp;lt; .05), with no changes in the corresponding control groups. Even when KAP was used without prescriptive feedback, smaller but significant mean falls in HbA1c of 0.7 and 0.8% (P &amp;lt; .05) were seen in IDDM and NIDDM patients, respectively, suggesting a motivational effect resulting from program participation. An inverse correlation was demonstrated between knowledge increment and final HbA1c in the ICT and KAP/feedback groups, which was significant for NIDDM patients (r = −.43, r = −.45; P &amp;lt; .05) but not for IDDM patients (r = − .2, r = .25;P=.1). Our studies confirm positive educational benefit of both computer-based programs, probably acting through enhancement of both knowledge and motivation.
Technique and Observation of Angular Gait Patterns in Running
Authors: K. Sykes
Journal: British Journal of Sports Medicine (1975)

A technique for the biomechanical analysis of running is described with specific reference to the angular displacement patterns of the lower limb. From high speed cine film recording profile views of the running gait, the Thigh, Knee and Ankle angles are measured during one complete cycle. Results are presented in the form of vector-space diagrams, namely Thigh-Knee angle and Knee-Ankle angle cyclograms. The diagrams are interpreted and some experimental observations are presented and discussed. The technique provides a useful research tool and a very good `teaching asset' for biomechanical studies of movement.
Identification of 6-Benzylthioinosine as a Myeloid Leukemia Differentiation–Inducing Compound
Authors: David N. Wald, Hanna M. Vermaat, Shaolei Zang, Andrew Lavik, Zizhen Kang, Gil Peleg, Stanton L. Gerson, Kevin D. Bunting, Munna L. Agarwal, Bryan L. Roth, William Tse
Journal: Cancer Research (2008)

Abstract As the pathophysiology of acute myelogenous leukemia (AML) involves a block of myeloid maturation, a desirable therapeutic strategy is to induce leukemic cell maturation to increase the efficacy and to avoid the side effects of traditional chemotherapeutics. Through a compound library screen, 6-benzylthioinosine (6BT) was identified as a promising differentiation-inducing agent. 6BT induces monocytic differentiation of myeloid leukemia cell lines such as HL-60 and OCI-AML3, as well as primary patient samples as evidenced by morphology, immunophenotyping, and nitroblue tetrazolium reduction. Not only can 6BT induce differentiation but a subset of AML cell lines such as MV4-11 and HNT34 instead undergo 6BT-mediated cell death. Despite inducing cell death in some leukemic cells, 6BT exhibits extremely low toxicity on several nonmalignant cells such as fibroblasts, normal bone marrow, and endothelial cells. This toxicity profile may relate to the function of 6BT as an inhibitor of the nucleoside transporter, ent1, which is thought to prevent it from entering many cell types. In contrast, 6BT likely enters at least some leukemic cell lines as shown by its requirement for phosphorylation for its differentiation activity. 6BT is also able to synergize with currently used myeloid differentiation agents such as ATRA and decitabine. Early studies indicate that the mechanism of action of this compound may involve ATP depletion that leads to growth inhibition and subsequent differentiation. Besides in vitro activity, 6BT also shows the ability to impair HL-60 and MV4-11 tumor growth in nude mice. 6BT is a promising new monocytic differentiation agent with apparent leukemic cell–specific activity. [Cancer Res 2008;68(11):4369–76]
Allelic genealogy and human evolution.
Authors: N Takahata
Journal: Molecular Biology and Evolution (1993)

Genetic variation at most loci examined in human populations indicates that the (effective) population size has been approximately 10(4) for the past 1 Myr and that individuals have been genetically united rather tightly. Also suggested is that the population size has never dropped to a few individuals, even in a single generation. These impose important requirements for the hypotheses for the origin of modern humans: a relatively large population size and frequent migration if populations were geographically subdivided. Any hypothesis that assumes a small number of founding individuals throughout the late Pleistocene can be rejected. Extraordinary polymorphism at some loci of the major histocompatibility complex (Mhc) rules out the past action of severe bottlenecks, or the so-called founder principle, which invokes only a small number of founding individuals when a new species emerges. This conclusion may be extended to the 35-Myr-old history of the human lineage, because some polymorphism at Mhc loci seems to have lasted that long. Furthermore, although the population structure prior to the late Pleistocene is less clear, owing to the insensitivity of Mhc alleles, even to low levels of migration, the nature of Mhc polymorphism suggests that the effective size of populations leading to humans was as large as 10(5). Hence, the effective population size of humans might have become somewhat smaller in most of the late Pleistocene. The reduction could be due either to the then adverse environment in the Old World and/or to the increased migration rate. It is also argued that population explosion fostered by the agriculture revolution has had significant effects on incorporating new alleles into human populations.