tbuckley/cabot-search huggingface dataset:
Abstract 2853: Genetic variation in IGF1, GHR, and IGFBP1 is associated with colorectal cancer
Authors: Elizabeth C. LeRoy, Elizabeth T. Jacobs, Erin L. Ashbeck, María Elena Martínez, Loic Le Marchand, Peter Lance, David Duggan, Patricia A. Thompson
Journal: Cancer Research (2010)

Abstract Background The insulin-like growth factor (IGF-1)/growth hormone (GH) pathway has been implicated in the development of colorectal cancer. Circulating IGF-1 increases cell proliferation and inhibits apoptosis. Genetic variation in the IGF pathway genes has been shown to alter circulating IGF-1 concentrations and has been associated with colorectal cancer. This risk may differ by anatomic location. Methods We used a principal components approach to evaluate the relationship between genetic variation in six IGF pathway genes (IGF1, IGF2, IGFBP1, IGFBP3, GHR, and GH1) and colorectal cancer in a family-based case-control study from the Colon Cancer Family Registry (CCFR). Cases were recruited from both high-risk clinics and population-based registries. Controls had no previous diagnosis of colorectal cancer and were full biologic siblings of the cases. Clinic-based (cases = 268, controls = 475) and population-based (cases = 1,802, controls = 2,874) data were analyzed separately and all models were adjusted for age and sex. Results There was no overall association between genetic variation in the IGF pathway genes and colorectal cancer. However, when the data were analyzed by colorectal cancer anatomic location, GH1 was associated with distal colon cancer (p=0.05) in the population-based families and IGF1 was associated with rectal cancer (p=0.004) in the clinic-based families. Furthermore, when the data were stratified by MSI-status, IGFBP1 was associated with MSI-low/stable tumors (p=0.017) in the clinic-based families. Conclusion In this family-based case-control study, genetic variation in IGF1, GHR, and IGFBP1 was associated with colorectal cancer differentially by anatomic location, population source, and tumor type. The clinic-based data represent families with high genetic risk in contrast to the population-based data which represent families of moderate to average genetic risk. These results replicate prior case-only analyses that suggest IGF1 is a modifier of colorectal cancer risk in high-risk families. Single SNP analyses and exploration of SNP x SNP interactions may further elucidate the significance of IGF pathway genes on colorectal cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2853.
Methadone Maintenance for Treatment of Addiction
Authors: Harris C. Faigel
Journal: JAMA (1971)

ABSTRACT To the Editor.— I disagree with the Goldstein and Brown (214:311-315, 1970) opinion that it is obvious... that methadone maintenance will now be adopted widely as the appropriate medical  for this condition. It is not all that clear to me.If drug dependency, like the top of an iceberg, is only a symptom of a personality in distress, then simply switching drugs will not produce any long range improvement. Many programs have done no more than this. I do not believe that methadone hydrochloride is therapy for heroin abuse any more than I believe that sutures are therapy for a laceration, but used as appropriate adjuncts to therapy, each has its place.At the present time I believe too little hard data have been collected. Dole and Nyswander's studies have been difficult to duplicate because selection criteria in other centers have often been too loose and personal supervision
Coronary Artery Bypass Graft Disease
Authors: Obi N. Nwasokwa
Journal: Annals of Internal Medicine (1995)

Purpose: To review saphenous vein graft disease and its prevention and management. Data Sources: A MEDLINE search of articles published on saphenous vein and arterial bypass grafts. Study Selection: The reference sections of articles focused the selection of key studies. Data Extraction: Relevant data representing key findings were noted. Data Synthesis: The outcome of coronary artery bypass grafting with the saphenous vein graft is unsatisfactory because vein grafts are prone to occlusive disease. By 10 years after surgery, 50% have closed, mainly because of atherosclerosis. With vein graft disease and graft closure, symptoms return. The best way to prevent vein graft disease is to use the internal mammary artery graft. This has become the preferred graft because it is not affected by atherosclerosis. Consequently, it has a much higher patency rate: 90% after more than 10 years. This provides such clinical benefits as decreased occurrence of symptoms, better left ventricular performance, decreased need for reoperation, and prolongation of life. The limited supply of mammary arteries has stimulated interest in identifying alternative arterial grafts. Conclusions: To prevent vein graft disease, surgeons should bypass diseased coronary arteries with at least one arterial graft and take measures during the surgery to avoid endothelial injury to vein grafts. Treatment with antiplatelet agents decreases the vein graft occlusion rate. When graft atherosclerosis causes symptoms, reoperation will probably prolong life if an old graft to the left anterior descending coronary artery is diseased. Reoperation increases a patient's chance for survival if the surgeon uses at least one arterial graft.
The Relationship of Gonadal Activity and Chemotherapy-Induced Gonadal Damage
Authors: Scott A. Rivkees
Journal: JAMA (1988)

We tested the hypothesis that chemotherapy-induced gonadal damage is proportional to the degree of gonadal activity during treatment. Thirty studies that evaluated gonadal function after cyclophosphamide therapy for renal disease or combination chemotherapy for Hodgkin's disease or acute lymphocytic leukemia provided data for analysis. Data were stratified according to sex, illness, chemotherapeutic regimen and dose, and pubertal stage at the time of treatment. Chemotherapy-induced damage was more likely to occur in patients who were treated when sexually mature compared with those who were treated when prepubertal. Males were significantly more frequently affected than females when treated for renal disease or Hodgkin's disease. Chemotherapy-induced damage was also more likely to occur when patients were treated with large doses of alkylating agents. These data suggest that chemotherapy-induced damage is proportional to gonadal activity. Further efforts are needed to test whether induced gonadal quiescence during chemotherapy will reduce the strikingly high incidence of gonadal failure following chemotherapy.
Developmental differences in IFN signaling affect GATA1s-induced megakaryocyte hyperproliferation
Authors: Andrew J. Woo, Karen Wieland, Hui Huang, Thomas E. Akie, Taylor Piers, Jonghwan Kim, Alan B. Cantor
Journal: Journal of Clinical Investigation (2013)

About 10% of Down syndrome (DS) infants are born with a transient myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20%-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). Somatic mutations leading to the exclusive production of a short GATA1 isoform (GATA1s) occur in all cases of DS-TMD and DS-AMKL. Mice engineered to exclusively produce GATA1s have marked megakaryocytic progenitor (MkP) hyperproliferation during early fetal liver (FL) hematopoiesis, but not during postnatal BM hematopoiesis, mirroring the spontaneous resolution of DS-TMD. The mechanisms that underlie these developmental stage-specific effects are incompletely understood. Here, we report a striking upregulation of type I IFN-responsive gene expression in prospectively isolated mouse BM- versus FL-derived MkPs. Exogenous IFN-α markedly reduced the hyperproliferation FL-derived MkPs of GATA1s mice in vitro. Conversely, deletion of the α/β IFN receptor 1 (Ifnar1) gene or injection of neutralizing IFN-α/β antibodies increased the proliferation of BM-derived MkPs of GATA1s mice beyond the initial postnatal period. We also found that these differences existed in human FL versus BM megakaryocytes and that primary DS-TMD cells expressed type I IFN-responsive genes. We propose that increased type I IFN signaling contributes to the developmental stage-specific effects of GATA1s and possibly the spontaneous resolution of DS-TMD.
Nontraumatic Plexitis and Heroin Addiction
Authors: Yasoma B. Challenor
Journal: JAMA (1973)

Brachial and lumbosacral plexitis were observed as new complications of intravenous injection of heroin-adulterant mixtures in 13 patients (eight with brachial and five with lumbosacral plexitis). Clinical features included monoparesis with impaired sensation and hyporeflexia in the involved limb. Severe causalgia-like pain was a frequent symptom for lowerextremity lesions. Electrodiagnostic studies showed denervation in the weak limb, with localization of the causative lesion at a plexus rather than at a radicular or peripheral nerve level in 12 patients. One patient showed a radicular localization. The lesions appeared to be at least partially reversible. A direct toxic effect of the injectant or hypersensitivity reactions are possible causes.
Estimation of swimmers' physical condition by a swimming recovery test.
Authors: P. Pilardeau, J. Vaysse, J. C. Engel, A. Jones, M. Garnier
Journal: British Journal of Sports Medicine (1983)

In this article, the authors propose an original analysis of the cardiac frequency after training. The study of rapid diminution (alactic oxygen debt) and of plateau (lactic debt in oxygen) make possible adjustment of the training. The variations observed in young swimmers during their sporting season and note a tangible improvement of the two components for recovery.
Transforming growth factor β signal transduction in hepatic stellate cells via Smad2/3 phosphorylation, a pathway that is abrogated during in vitro progression to myofibroblasts
Authors: M. Stopa, M. Streckert, L. Bonzel, B. Delvoux, P. ten Dijke, A.M. Gressner, S. Dooley
Journal: Journal of Hepatology (2001)
The Harveian Oration on Gilbert, Bacon, and Harvey
Authors: W. Hale-White
Journal: BMJ (1927)

THERE are two reasons why Harvey should be placed in the select class of really great men.One is, because he discovered that the blood circiulates, being compelled to do so by the contraction of-the heart;`the other-even more powerful-is, because he was among the earlier scientists to show the value of properly conducted experiment.
Fibreoptic endoscopy and the barium meal--results and implications.
Authors: P B Cotton
Journal: BMJ (1973)

The other story is that the tumour may be a teratoma and arise from germinomatous cells which tend to occur in the midline-mediastinum, ovaries, testis, and so on.Many of these tumours have teratomatous elements such as cartilage, muscle, or thyroid-but this one did not.Table II shows a histochemical comparison between cells from a pinealoma, seminoma of the testis, and normal pineal gland.Both tumours contained alkaline phosphatase in the large cells.None was present in cells of the normal pineal gland.This is not a common enzyme and is usually associated with specific cell function.It is probably not a chance finding.So the argument remains unresolved.
Accreditation as a Stabilizing Force in Allied Health Professions
Authors: John R. Proffitt
Journal: JAMA (1970)

In approaching this subject, I think that it might first be in order to ask ourselves some questions about this thing which we call accreditation, how it has come into being, and where it is going. We of the Accreditation and Institutional Eligibility staff of the Office of Education define accrediting as follows: the process whereby an association or agency grants public recognition to a school, institute, college, university, or specialized program of study having met certain established qualifications of standards as determined through initial and periodic evaluations. Increasingly, accrediting also infers stimulation toward quality improvement beyond the minimum standards specified by the accrediting body. On the other hand, one noted authority, Dr. William Selden, former executive director of the National Commission on Accrediting, refers to accreditation as basically a struggle over standards in education. The implication here is that this is a struggle conducted largely by competing groups of
Abstract 659: Overexpression of TPX2 accelerates cell cycle progression in melanoma and is an indicator of response to Aurora A kinase inhibitors
Authors: Bin Li, M. Dalla Palma, K. L. Nathanson, G. Xu, K. Smalley, M. Herlyn
Journal: Cancer Research (2010)

Abstract There is a tremendous need to identify more effective treatments for metastatic melanoma. In order to detect genetic changes in melanoma that might facilitate the development of novel therapies, we performed aCGH in melanoma cell lines and tumors and identified that Targeting Protein for Xklp2 (TPX2) was the most commonly amplified gene on 20q11.21, a region of frequent gain. Gene expression profiling studies also demonstrated overexpression of TPX2, suggesting a previously unknown role in the development of melanoma. TPX2 is a microtubule-associated protein that regulates bipolar spindle assembly and centrosome replication; the TPX2 - Aurora A interaction is essential for accurate segregation of chromosome and mitosis progression. We evaluated a potential role for TPX2 overexpression in melanoma using TPX2 overexpressing melanoma cell lines as a model. TPX2 overexpressing cell lines display accelerated cell cycle progression, increased CDK1/CDK2 activity, cyclin A/B1 levels, and constitutive activation and overexpression of Aurora A. We depleted TPX2 using shRNA to further dissect its role in melanoma. In unsynchronized cells, TPX2 depletion causes prolonged mitotic arrest accompanied by persistent activation of the spindle-assembly checkpoint (SAC) and caspase-3, and subsequent caspase-dependent cell death. In contrast, with G1/S synchronization, TPX2 depletion decreases S phase entry and delays S-G2-M phase transition followed by marked cell death. Accordingly, TPX2 depletion was associated with decreased CDK1 activity but not CDK2 activity, and activation of caspase and low activation of the SAC. Our data demonstrate that TPX2 overexpression is required for increased CDK1-cyclinB1 activity, thus accelerating cell cycle progression. Accordingly, TPX2-overexpressing melanoma cell lines are dependent on TPX2 for proliferation, whereas non-overexpressing cell lines and melanocytes are not. Additionally, TPX2-overexpressing cell lines are 3-10 time more sensitive to an Aurora A kinase inhibitor (VX680) than non-overexpressing cell line, suggesting that TPX2-activating Aurora A kinase could become a novel therapeutic target for treatment of melanoma with highly expressed TPX2, Finally, TPX2-IHC staining demonstrated that a significantly increased expression of TPX2 in primary and metastatic melanoma as compared to begin nevi, suggesting it is a marker of progression. Thus, we have identified TPX2 as a novel gene upregulated in melanoma. Overexpression of TPX2 may be a marker of tumors sensitive to Aurora A inhibitors allowing patient stratification for optimal therapeutic selection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 659.
Antibody-induced modulation of the CD3/T cell receptor complex causes T cell refractoriness by inhibiting the early metabolic steps involved in T cell activation.
Authors: G Pantaleo, D Olive, A Poggi, T Pozzan, L Moretta, A Moretta
Journal: The Journal of Experimental Medicine (1987)

We investigated the mechanism involved in T cell unresponsiveness that follows the monoclonal antibody-induced surface modulation of the CD3-TCR complex. We determined whether modulation of CD3-TCR affected the early metabolic steps such as [Ca2+]i rise and InsP3 formation. A strong inhibition of the increase on [Ca2+]i mediated by either anti-TCR or anti-CD2 mAbs was detected. In contrast, surface modulation of CD2 molecules did not prevent the [Ca2+]i increase induced by anti-TCR mAb. Similarly, InsP3 increase was strongly reduced only after modulation of CD3-TCR complex (but not of CD2 molecules). Therefore, it appears that surface modulation of CD3-TCR complex causes T cell refractoriness by inhibiting the very early metabolic events that follow receptor-ligand interactions.
MORTALITY, EARLY AND LATE, FOLLOWING CESAREAN SECTION
Authors: FREDERICK H. FALLS
Journal: JAMA (1942)

When in the course of pregnancy or labor it becomes necessary to consider delivery by cesarean section as the best way to minimize the danger which is present in an individual case, the various methods of delivery from below must be carefully compared in order to evaluate their dangers to mother and baby under the peculiar exigencies of the situation. A careful weighing of the possibilities for each method of delivery is mandatory in order to avoid unnecessary risk. This can be done effectively only by a physician thoroughly trained in obstetrics. It is possible for one with sufficient general surgical skill to operate on the mother, to obtain a live baby and to have the mother also survive. Practically, however, it is found that in many instances the operation might have been avoided if the strictest indications had been observed and operative intervention delayed until absolute necessity dictated it.
Considerations for the Clinical Application of Chimeric Antigen Receptor T Cells: Observations from a<i>Recombinant DNA Advisory Committee Symposium</i>Held June 15, 2010
Authors: Hildegund C.J. Ertl, John Zaia, Steven A. Rosenberg, Carl H. June, Gianpietro Dotti, Jeffrey Kahn, Laurence J.N. Cooper, Jacqueline Corrigan-Curay, Scott E. Strome
Journal: Cancer Research (2011)

Abstract T cells that are genetically modified to express single-chain chimeric antigen receptors (CAR) have shown promise in early cancer immunotherapy clinical trials. Unfortunately, 2 recent deaths in cancer patients treated with CAR T cells have created some uncertainty on how to best mitigate patient risk, while continuing to advance this very promising therapeutic avenue. In order to address these concerns, the Recombinant DNA Advisory Committee (RAC) held a symposium, the objectives of which were to first review the reported treatment-associated toxicities and, second, to discuss methods for improving safety and efficacy. This report highlights the issues raised as part of this discussion, with a specific focus on protocols infusing CAR T cells. Because this was not a consensus conference, the opinions described should not be construed to represent those of any individual RAC member, the RAC as a body, conference participants, the National Institutes of Health, or the U.S. Food and Drug Administration. Cancer Res; 71(9); 3175–81. ©2011 AACR.
Mutational bias provides a model for the evolution of Huntington's disease and predicts a general increase in disease prevalence
Authors: David C. Rubinsztein, William Amos, Jayne Leggo, Sandy Goodburn, Rajkumar S. Ramesar, John Old, Ronald Bontrop, Robert McMahon, David E. Barton, Malcolm A. Ferguson-Smith
Journal: Nature Genetics (1994)
Abstract S4-4: Independent validation of Genomic Grade in the BIG 1-98 study
Authors: C Sotiriou, M Ignatiadis, C Desmedt, Jr HA Azim, I Veys, D Larsimont, M Lyng, G Viale, B Leyland-Jones, H Ditzel, A Giobbie-Hurder, M Regan, M Piccart, S Michiels
Journal: Cancer Research (2012)

Abstract Background: We have reported that a 97-gene signature, the Genomic Grade Index (GGI) can separate histological grade (HG) 2 breast tumors into low vs high GGI tumors with different outcomes. We have also developed a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) tool including 6 reporter and 3 control genes that can reliably evaluate Genomic Grade (GG) in paraffin embedded tumors. Methods: We evaluated the qRT-PCR GG in women treated with either tamoxifen or letrozole monotherapy in the Breast International Group (BIG) 1–98 study with 8.1 year median follow-up. The association between continuous GG and distant recurrence-free interval (DRFI) was evaluated in Cox regression models stratified for the 2 vs 4 arm randomization option, chemotherapy and hormonotherapy use, with and without adjustment for clinicopathological characteristics. Estrogen, progesterone receptor (ER, PR), Ki67 and HG were centrally reviewed. The clinicopathological model included age and log2 tumor size, ER and PR as continuous variables, nodal status (N0 vs 1–3 vs &amp;gt;3), HG (1 vs 2 vs 3) and HER2 (negative vs positive). Similar analyses were performed for log2 Ki67 as continuous variable. Added prognostic value was assessed using the likelihood ratio statistic. Results: We obtained GG in 883 (62%) of 1428 samples. Non evaluable results were due to pre-analytical issues or technical failure. Among the 883 patients, 521 (59%) had N0 disease, 435 (49%) were treated with tamoxifen and 84 (10%) had distant recurrences. The GG classified 502 patients with HG2 tumors as either GG1 (N = 202, 40%), equivocal (N = 220, 44%) or GG3 (N = 80, 16%). In univariate analysis, increasing GG and Ki67 were significantly associated with lower DRFI (Table). When the 773 N0/1-3 patients were analyzed based on HG, the Kaplan-Meier estimate for 10-year DRFI was 98% (95% confidence intervals 96–100%) for the 123 HG1, 92% (88–95%) for the 456 HG2 and 84% (78–90%) for the 194 HG3 patients. In the N0/1-3 population, 10 year DRFI based on GG was 95% (96–100%) for the 290 GG1, 92% (89–95%) for the 309 GG equivocal and 84% (77–90%) for the 178 GG3 patients. Interestingly, when the 456 HG2 and N0/1-3 patients were analyzed based on GG, the 10-year DRFI was 95% (92–100%) for the 185 HG2/GG1 patients, 92% (88–96%) for the 202 HG2/GG equivocal patients, 86% (76–96%) for the 69 HG2/GG3 patients. In all patients either GG or Ki67 as continuous variable significantly improved the clinicopathological model in predicting distant recurrence (Table). Conclusion: Either Genomic Grade or centrally reviewed Ki67 provides independent prognostic information for risk of distant recurrence beyond clinicopathological characteristics in patients treated with endocrine therapy. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S4-4.
Variations in 35SO4 incorporation into glycosaminoglycans along canine coronary arteries. A possible index of artery wall stress.
Authors: R J Boucek, N L Noble, D E Wells
Journal: Circulation Research (1976)

Focal areas of accentuated wall stress along the course of canine coronary arteries may be revealed by the level of 35SO4 incorporation into glycosaminoglycans (GAG). In the anterior descending artery, 35SO4 incorporation in higher in the proximal than in the distal region and may be extraordinarily high as the vessel enters a proximally located muscle bridge and at the takeoff region of multidirectional branches. In the circumflex artery, the incorporation also is higher in the proximal than in the distal region and is high at the genu where the posterior descending artery forms. There are differences in uptake of 35SO4 in vessels even when the arteries arise from the same vascular bed.this was shown by the higher incorporation in the left coronary artery than in the right coronary artery. A general anatomical agreement exists between these sites of high 35SO4 incorporation and previously described locations of interval elastic disruption ans proliferation of intimal connective tissue in the dog.