tbuckley/cabot-search huggingface dataset:
Mutant lines of guinea pig L2C leukemia. I. Deletion of Ia alloantigens is associated with a loss in immunogenicity of tumor-associated transplantation antigens.
Authors: G Forni, E M Shevach, I Green
Journal: The Journal of Experimental Medicine (1976)

Five different lines of a strain 2 guinea pig leukemia (L2C) which had been carried in different laboratories share certain chromosomal markers and have a common surface immunoglobulin idiotypic determinant indicating that they have a common origin. All these leukemic lines have on their surface of the B alloantigen (equivalent of the murine H-2K and H-2D antigens) and four of these five lines have on their surface the Ia alloantigens normally present on the strain 2 lymphocytes. The result of a study of the growth and rejection patterns of these leukemias in inbred and random-bred guinea pigs of selected histocompatibility type indicates that both the B and Ia antigens can act as transplantation antigens in guinea pigs. Immunization protection tests in syngeneic animals demonstrated that the four Ia-positive leukemias possessed a tumor-associated transplantation antigen (TATA), while the one Ia-positive leukemias possessed a tumor-associated transplantation antigen (TATA), while the one Ia-negative leukemia by this criteria did not appear to have TATA. However, crisscross immunization protection tests demonstrated that preimmunization of syngeneic animals with an Ia-positive L2C line lead to a subsequent protection against challenge with the Ia-negative leukemia. Immunization with the Ia-negative line never protected against a subsequent challenge with any of the leukemic cells of L2C lines. These results strongly suggest that the Ia-negative leukemia possessed a TATA that can be recognized but is not itself immunogenic, and also indicate that Ia antigens on L2C cells are functionally associated with TATA and can act as immunological carries for tumor transplantation determinants.
Assessment of Glucose Tolerance Test Criteria for Diagnosis of Diabetes in Chinese Subjects
Authors: Clive S Cockram, Joseph T F Lau, Albert Y W Chan, Jean Woo, Ramasamyiyer Swaminathan
Journal: Diabetes Care (1992)

OBJECTIVE To examine and compare WHO diagnostic criteria for diabetes mellitus. RESEARCH DESIGN AND METHOD The relationship between FPG and 2-h glucose are examined in 680 OGTTs with a quadratic regression model and ROC analysis. Simultaneous measurements of HbA1 and fructosamine are also compared with multiple linear regression. RESULTS Two hundred eighteen subjects (32%) had 2-h glucose ≥ 11.1 mM, of which only 86 had FPG ≥ 7.8 mM. Only 2 subjects had FPG &amp;gt; 7.8 mM and 2-h glucose &amp;lt; 7.8 mM. Of subjects with 2-h glucose &amp;lt; 7.8 mM (n = 332), only 9 had FPG &amp;gt; 6.0 mM. From the quadratic model, the predicted FPG corresponding to 2-h glucose = 11.1 mM was 5.7 mM, whereas the predicted 2-h glucose corresponding to FPG = 7.8 mM was 15.2 mM. ROC analysis showed that, with 2-h glucose ≥ 11.1 mM as indicating diabetes, an FPG of 5.6 mM gave an intersect for sensitivity and specificity of 87%. HbA1 and fructosamine correlated more closely with 2-h glucose and area under the OGTT curve than with FPG. CONCLUSIONS Given that a 2-h glucose cutoff of 11.1 mM can be justified from other studies, our results suggest that the FPG cutoff of 7.8 mM when used for screening purposes should be reduced. At a suggested value of 7.0 mM, specificity remains 98.5%, whereas sensitivity increases to 57%.
Ventricular Septal Aneurysms
Authors: JOSEF EDELSTEIN, BERNARD L. CHARMS
Journal: Circulation (1965)

Two cases of ventricular septal aneurysm are reported, one in the membranous septum and one in the muscular portion. The diagnosis was made by selective left ventricular angiography. It is suggested that these cases represent spontaneous closure of a ventricular septal defect with weakness and aneurysmal [see table in the PDF file] formation due to the high left ventricular pressure. Both are asymptomatic and hemodynamically within normal limits. Surgical repair of the aneurysms is not considered necessary.
Optical Biopsy of Bladder Cancer Using Crowd-Sourced Assessment
Authors: Stephanie P. Chen, Sarah Kirsch, Dimitar V. Zlatev, Timothy Chang, Bryan Comstock, Thomas S. Lendvay, Joseph C. Liao
Journal: JAMA Surgery (2015)

This study assesses the use of confocal laser endomicroscopy to diagnose and grade bladder cancer and applied crowdsourcing to determine the barriers to learning how to diagnose cancer using confocal laser endomicroscopy.
Functional role of endothelial adhesion molecules in the early stages of brain metastasis
Authors: Manuel Sarmiento Soto, Sébastien Serres, Daniel C. Anthony, Nicola R. Sibson
Journal: Neuro-Oncology (2013)

Cellular adhesion molecules (CAMs), which are normally associated with leukocyte trafficking, have also been shown to play an essential role in tumor metastasis to non-CNS sites. However, the role played by CAMs in brain metastasis is largely unexplored. It is known that leukocyte recruitment to the brain is very atypical and that mechanisms of disease in peripheral tissues cannot be extrapolated to the brain. Here, we have established the spatiotemporal expression of 12 key CAMs in the initial phases of tumor seeding in 2 different models of brain metastasis. BALB/c or SCID mice were injected intracardially (105 cells/100 μL phosphate-buffered saline with either 4T1-GFP or MDA231BR-GFP cells, respectively (n = 4–6/group), and expression of the CAMs was determined by immunohistochemistry and immunofluorescence colocalisation. Endothelial expression of E-selectin, VCAM-1, ALCAM, ICAM-1, VLA-4, and β4 integrin was markedly increased early in tumor seeding. At the same time, the natural ligands to these adhesion molecules were highly expressed on the metastatic tumor cells both in vitro and in vivo. Two of these ligands showed particularly high tumor cell expression (ALCAM and VLA-4), and consequently their functional role in tumor seeding was determined. Antibody neutralization of either ALCAM or VLA-4 significantly reduced tumor seeding within the brain (>60% decrease in tumor number/mm2 brain; P < .05–0.01). These findings suggest that ALCAM/ALCAM and VLA-4/VCAM-1 interactions play an important functional role in the early stages of metastasis seeding in the brain. Moreover, this work identifies a specific subset of ligand-receptor interactions that may yield new therapeutic and diagnostic targets for brain metastasis.
Effects of Coronary Bypass Graft Occlusion on Left Ventricular Performance
Authors: RICHARD P. ANDERSON
Journal: Circulation (1972)

High-fidelity recordings of left ventricular (LV) pressure and its corresponding first derivative (dP/dt), electrocardiogram, and systemic arterial pressure were obtained intraoperatively following insertion of aortocoronary saphenous vein bypass grafts in eight men. During sequential 3-min periods, the bypass grafts were, in turn, open, occluded by vascular clamps, and opened by releasing the clamps. Peak dP/dt averaged 1342 mm Hg/sec before graft occlusion, fell to 1223 mm Hg/sec during occlusion, and rose following release of occlusion to 1373 mm Hg/sec. LV end-diastolic pressure (LVEDP) averaged 14.5 mm Hg before, 17.6 mm Hg during, and 16.1 mm Hg after graft occlusion. Arterial systolic and diastolic pressure and heart rate showed little change ( P &gt; 0.05) throughout the experiments. Left ventricular performance as gauged by peak dP/dt/LVEDP decreased an average of 25% ( P &lt; 0.001) during graft occlusion and returned to control levels following release of occlusion. Total vein graft blood flow, measured immediately before the occlusion experiments, averaged 164 ml/min. Good correlation was lacking between vein graft blood flow and performance changes during graft occlusion in individual patients. Aortocoronary vein bypass grafts are capable of participating directly in the mechanical events of the cardiac cycle. Acute graft occlusion can impair, while restoration of graft flow can improve, left ventricular performance.
Secondhand Tobacco Smoke in Public Places in Latin America, 2002-2003
Authors: Ana Navas-Acien
Journal: JAMA (2004)

The success of measures to restrict smoking in indoor environments and the intensity of enforcement vary among countries around the world. In 2001, the Pan American Health Organization (PAHO) launched the Smoke-Free Americas Initiative to build capacity to achieve smoke-free environments in Latin America and the Caribbean.To assess secondhand smoke concentrations in public places in the capital cities of Argentina, Brazil, Chile, Costa Rica, Paraguay, Peru, and Uruguay in conjunction with the Smoke-Free Americas Initiative.Multicountry assessment of vapor-phase nicotine concentrations using a common protocol in all 7 Latin American countries. A total of 633 sampling devices were placed for 7 to 14 days in 1 hospital, 2 secondary schools, 1 city government building, 1 airport (2 in Argentina), and restaurants and bars in each country.Concentrations of airborne nicotine.Airborne nicotine was detected in most (94%) of the locations surveyed. By country, Argentina and Uruguay had the highest median concentrations in most environments (eg, in hospitals: 1.33 [interquartile range [IQR], 0.51-3.12] microg/m3 and 0.8 [IQR, 0.30-1.69] microg/m3, respectively). Overall, bars and restaurants had the highest median concentrations (3.65 [IQR, 1.55-5.12] microg/m3 and 1.24 [IQR, 0.41-2.48] microg/m3, respectively). Nicotine concentrations were also found in a number of key, sentinel buildings, including 95% (155/163) of hospital samples (in the physicians' and nurses' stations the median was 0.27 [IQR, 0.02-1.94] microg/m3), schools, government buildings, and/or airports in most countries.The finding of airborne nicotine in critical locations in Latin America provides a basis for enforcing smoke-free initiatives and for strengthening the protection of the public from unwanted exposure to secondhand smoke.
Seliciclib (CYC202 or R-roscovitine), a small-molecule cyclin-dependent kinase inhibitor, mediates activity via down-regulation of Mcl-1 in multiple myeloma
Authors: Noopur Raje, Shaji Kumar, Teru Hideshima, Aldo Roccaro, Kenji Ishitsuka, Hiroshi Yasui, Norihiko Shiraishi, Dharminder Chauhan, Nikhil C. Munshi, Simon R. Green, Kenneth C. Anderson
Journal: Blood (2005)

Abstract Cyclin-dependent kinase (CDK) inhibitors have the potential to induce cell-cycle arrest and apoptosis in cancer cells. Seliciclib (CYC202 or R-roscovitine) is a potent CDK inhibitor currently undergoing phase-2 clinical testing in lung and B-cell malignancies. Here we studied the in vitro cytotoxic activity of seliciclib against multiple myeloma (MM) cells. Our data demonstrate that seliciclib has potent cytotoxicity against MM cells that are both sensitive and resistant to conventional therapy as well as primary MM cells from patients. Cell-cycle and Western blot analysis confirmed apoptosis. Importantly, seliciclib triggered a rapid down-regulation of Mcl-1 transcription and protein expression independent of caspase cleavage. Adherence of MM cells to bone marrow stromal cells (BMSCs) induced increased Mcl-1 expression associated with signal transducer and activator of transcription 3 (STAT3) phosphorylation, which was inhibited in a time- and dose-dependent manner by seliciclib. Furthermore, seliciclib inhibited interleukin 6 (IL-6) transcription and secretion triggered by tumor cell binding to BMSCs. Up-regulation of Mcl-1 expression in cocultures was only partially blocked by neutralizing antibody to IL-6, suggesting alternative mechanisms of Mcl-1 modulation by seliciclib. Finally, combination studies of seliciclib with doxorubicin and bortezomib show in vitro synergism, providing the rationale for testing these drug combinations to improve patient outcome in MM.
"WE HAVE REASON TO THINK..."
Authors: W. L. Brown
Journal: BMJ (1935)

I doubly appreciate the honour of being asked to give the prizes here to-day.In the first place it emphasizes the association which has lasted so long between my univer- sity and your hospital.We have recently benefited by the munificent bequest of one who was a loyal son of Cambridge and who also served this hospital well; I mean the late Mr. Marmaduke Sheild.Through that bequest we have been able, among other things, to re- establish pharmacology in its proper place, and we con- fidently expect that Professor Verney will continue the successful-work of that department, which owed so much in the past to the late Dr. W. E. Dixon.In the second place it emphasizes another association: that between my hospital of St. Bartholomew's and yours.That we have sent you good men the past and the present attest alike.At the present time my pre-
Extracellular K+ and Opening of Voltage-Gated Potassium Channels Activate T Cell Integrin Function
Authors: Mia Levite, Liora Cahalon, Asher Peretz, Rami Hershkoviz, Alex Sobko, Amiram Ariel, Rooma Desai, Bernard Attali, Ofer Lider
Journal: The Journal of Experimental Medicine (2000)

Elevated extracellular K+ ([K+]o), in the absence of “classical” immunological stimulatory signals, was found to itself be a sufficient stimulus to activate T cell β1 integrin moieties, and to induce integrin-mediated adhesion and migration. Gating of T cell voltage-gated K+ channels (Kv1.3) appears to be the crucial “decision-making” step, through which various physiological factors, including elevated [K+]o levels, affect the T cell β1 integrin function: opening of the channel leads to function, whereas its blockage prevents it. In support of this notion, we found that the proadhesive effects of the chemokine macrophage-inflammatory protein 1β, the neuropeptide calcitonin gene–related peptide (CGRP), as well as elevated [K+]o levels, are blocked by specific Kv1.3 channel blockers, and that the unique physiological ability of substance P to inhibit T cell adhesion correlates with Kv1.3 inhibition. Interestingly, the Kv1.3 channels and the β1 integrins coimmunoprecipitate, suggesting that their physical association underlies their functional cooperation on the T cell surface. This study shows that T cells can be activated and driven to integrin function by a pathway that does not involve any of its specific receptors (i.e., by elevated [K+]o). In addition, our results suggest that undesired T cell integrin function in a series of pathological conditions can be arrested by molecules that block the Kv1.3 channels.
Angiotensin stimulates glucose and fluid absorption by rat proximal straight tubules.
Authors: J L Garvin
Journal: Journal of the American Society of Nephrology (1990)

I investigated the effect of angiotensin on glucose and fluid absorption by isolated, perfused rat proximal straight tubules. During the control period, tubules absorbed fluid at 0.68 +/- 0.05 nL/mm.min and glucose at 12.5 +/- 1.3 pmol/mm.min. After 10(-10) M angiotensin was added to the bath, tubules absorbed fluid at 0.82 +/- 0.06 nL/mm.min and glucose at 16.0 +/- 2.4 pmol/mm.min--a stimulation of both parameters by 30%. Time controls showed no significant change in the rate of glucose or fluid absorption. This stimulation was due to an increase in the maximum rate of transport. The maximum rate of glucose absorption with 5.5 mM in bath and perfusate increased from 14.5 +/- 1.6 pmol/mm.min to 18.5 +/- 1.4 pmol/mm.min after 10(-10) M angiotensin was added to the bath. In contrast, the Km for glucose did not change, since a solution containing 0.55 mM glucose (approximately Km) supported 63 +/- 6% of the maximum rate during the control period and 60 +/- 5% of the maximum rate after angiotensin was added to the bath. Angiotensin also had no effect on glucose permeability, which was (3.7 +/- 0.4) x 10(-6) cm/s before treatment and (3.8 +/- 0.4) x 10(-6) cm/s after treatment. From these data, it is concluded that: (1) angiotensin stimulates glucose absorption in the rat proximal straight tubule; (2) this stimulation is the result of an increase in the maximum rate of transport rather than a change in Km or permeability; and (3) stimulation of Na/glucose absorption by angiotensin accounts for a significant portion of the increase in fluid absorption caused by angiotensin.
Biological Role and Potential Therapeutic Targeting of the Chemokine Receptor CXCR4 in Undifferentiated Thyroid Cancer
Authors: Valentina De Falco, Valentina Guarino, Elvira Avilla, Maria Domenica Castellone, Paolo Salerno, Giuliana Salvatore, Pinuccia Faviana, Fulvio Basolo, Massimo Santoro, Rosa Marina Melillo
Journal: Cancer Research (2007)

Abstract Anaplastic thyroid carcinoma (ATC) is a rare thyroid cancer type with an extremely poor prognosis. Despite appropriate treatment, which includes surgery, radiotherapy, and chemotherapy, this cancer is invariably fatal. CXCR4 is the receptor for the stromal cell–derived factor-1 (SDF-1)/CXCL12 chemokine and it is expressed in a variety of solid tumors, including papillary thyroid carcinoma. Here, we show that ATC cell lines overexpress CXCR4, both at the level of mRNA and protein. Furthermore, we found that CXCR4 was overexpressed in ATC clinical samples, with respect to normal thyroid tissues by real-time PCR and immunohistochemistry. Treatment of ATC cells with SDF-1 induced proliferation and increase in phosphorylation of extracellular signal–regulated kinases and protein kinase B/AKT. These effects were blocked by the specific CXCR4 antagonist AMD3100 and by CXCR4 RNA interference. Moreover, AMD3100 effectively reduced tumor growth in nude mice inoculated with different ATC cells. Thus, we suggest that CXCR4 targeting is a novel potential strategy in the treatment of human ATC. [Cancer Res 2007;67(24):11821–9]
Genetic control of sebum excretion and acne—a twin study
Authors: SHERNAZ WALTON, E.H. WYATT, W.J. CUNLIFFE
Journal: British Journal of Dermatology (1988)

Sebum excretion and acne grades were measured in 20 pairs each of identical and non‐identical like‐sex twins. The identical twins had virtually identical rates of sebum excretion (P > 0·05), but they had a significantly different degree of acne severity (P < 0·01). The non‐identical twins had significantly different sebum excretion rates (P > 0·01) and acne grades (P < 0·01). These findings suggest that sebum excretion is under genetic control and the development of clinical lesions is modified by environmental factors.
Real-time assessment of myocardial perfusion and wall motion during bicycle and treadmill exercise echocardiography: comparison with single photon emission computed tomography
Authors: Sarah Shimoni, William A Zoghbi, Feng Xie, David Kricsfeld, Sherif Iskander, Lisa Gobar, Issam A Mikati, John Abukhalil, Mario S Verani, Edward L O’Leary, Thomas R Porter
Journal: Journal of the American College of Cardiology (2001)
Modulation of triggered activity by uncoupling in the ischemic border A model study with phase 1b-like conditions
Authors: A Pollard
Journal: Cardiovascular Research (2002)

Objective: Triggered beats during regional ischemia may depend upon the electrical source and sink charge interactions between adjacent regions of normal and ischemic cardiac tissue that are partly controlled by electrical coupling. Methods: To study these relationships, we modified parameters in the Luo–Rudy dynamic membrane equations to reflect physiologic conditions associated with phase 1b arrhythmias. Superthreshold delayed afterdepolarizations (DADs) formed after pacing. Coupling contributions were then examined using: (i) a single phase 1b myocyte connected via a variable resistance to a single normal myocyte, and (ii) a multicellular fiber with a 1-cm segment of phase 1b myocytes connected to a 1-cm normal segment having resistance changes that were confined to the ischemic segment. Integration of ionic, capacitive and coupling currents during DAD initiation allowed charge quantification. Results: In cell pairs, phase 1b myocyte DADs were suppressed at resistances where normal myocyte pacing resulted in phase 1b myocyte excitation. Coupling charge requirements limited capacitive charging in the phase 1b myocyte, which occurred in combination with diastolic hyperpolarization that shifted transmembrane potential from threshold. In multicellular fiber simulations, DADs were suppressed with strong coupling in the phase 1b segment. Moderate uncoupling of that segment allowed superthreshold DAD formation away from the border that initiated action potential propagation in the normal segment. With severe uncoupling, propagation failed at the border. Conclusions: These findings support the clinical and experimental observation that intermediate uncoupling is an important contributor to phase 1b arrhythmogenesis.
A Trial of Prazosin for Combat Trauma PTSD With Nightmares in Active-Duty Soldiers Returned From Iraq and Afghanistan
Authors: Murray A. Raskind, Kris Peterson, Tammy Williams, David J. Hoff, Kimberly Hart, Hollie Holmes, Dallas Homas, Jeffrey Hill, Colin Daniels, Jess Calohan, Steven P. Millard, Kirsten Rohde, James O’Connell, Denise Pritzl, Kevin Feiszli, Eric C. Petrie, Christopher Gross, Cynthia L. Mayer, Michael C. Freed, Charles Engel, Elaine R. Peskind
Journal: American Journal of Psychiatry (2013)

The authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan.Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7 mg of prazosin (SD=0.5) and 2.0 mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning. Secondary outcome measures were the 17-item CAPS, the Hamilton Depression Rating Scale, the Patient Health Questionnaire-9, and the Quality of Life Index. Maintenance psychotropic medications and supportive psychotherapy were held constant.Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups.Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.