tbuckley/cabot-search huggingface dataset:
Abstract 1130: Antitumor activity of a pyrrole-imidazole polyamide in three tumor xenograft models.
Authors: Nicholas G. Nickols, Fei Yang, Benjamin C. Li, Georgi K. Marinov, Jonathan W. Said, Peter B. Dervan
Journal: Cancer Research (2013)

Abstract Background: Pyrrole-imidazole polyamides are synthetic minor groove binders with modular sequence recognition. We developed a polyamide that targets the DNA sequence 5’-WGWWCW-3’ (W=A/T). This molecule is cytotoxic in a number of cancer cell lines including LNCaP (prostate cancer), DU145 (prostate cancer), and A549 (lung cancer). Data in cell culture suggests that this molecule interferes with RNA polymerase 2 activity resulting in proteasome-mediated degradation of the RNA Polymerase 2 large subunit, activation of p53 and induction of p53 target genes, and apoptosis. This polyamide demonstrates no detectable DNA damage by alkaline comet assay nor does it induce detectable phosphorylation of γH2A.X, ATM, DNA-PKcs, p53, or Chk2. This polyamide circulates in mice after intravenous and subcutaneous injection in saline vehicle. Methods: Male immune compromised mice were implanted with LNCaP, DU145, or A549 tumors. Tumors were allowed to grow until approximately 100 mm3 and then stratified into vehicle (5% DMSO/PBS) and treatment arms (1 mg/kg polyamide, in vehicle). Treatment was administered via subcutaneous injection every three days, for a total of three cycles (LNCaP), eight cycles (DU145), or six cycles (A549). At the experimental endpoint, tumors were resected and weighed immediately. For LNCaP xenografts, serum PSA pre- and post-treatment were also measured. In parallel, a group of immune compromised mice without xenografts were treated with an identical regimen for eight cycles and subsequently observed for three months. Results: Tumors resected from polyamide-treated mice were statistically smaller than those of vehicle-treated mice. The effect was greatest on LNCaP tumors (n=12, Treated (T)/Control (C): 32%, p=1.6E-5). DU145 tumors (n=6, T/C: 34%, p=0.013), and A549 tumors (n=8, T/C: 62%, p=0.047) were also affected. Post-treatment serum PSA in the polyamide-treated mice with LNCaP xenografts were lower than for the vehicle treated mice (p = 0.024). Statistical differences between treated and control groups were determined using two-tailed t-tests. Polyamide treatment resulted in no significant weight loss or observable distress in tumor-free mice and these mice appeared healthy for at least three months after treatment was complete. Conclusions: The polyamide demonstrated in vivo antitumor activity in this panel of tumor xenografts with limited host toxicity. Citation Format: Nicholas G. Nickols, Fei Yang, Benjamin C. Li, Georgi K. Marinov, Jonathan W. Said, Peter B. Dervan. Antitumor activity of a pyrrole-imidazole polyamide in three tumor xenograft models. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1130. doi:10.1158/1538-7445.AM2013-1130
Saccular aneurysm caused by bacterial endocarditis in a syphilitic aorta
Authors: W. M. Robinson, I. K. R. McMillan, A. M. Johnson
Journal: Thorax (1973)

<b>Robinson, W.M., McMillan, I.K.R., and Johnson, A. M. (1973)</b>. <i>Thorax</i>, 529-532. <b>Saccular aneurysm caused by bacterial endocarditis in a syphilitic aorta</b>. The rapid development of a saccular aneurysm during successfully treated bacterial endocarditis, in an ascending aorta previously affected by syphilis which had been treated with adequate chemotherapy 15 years previously, is described. Although bacterial endocarditis does occasionally complicate syphilitic aortic valve disease, the literature does not contain any report of resulting aneurysm development. The investigation and successful surgical treatment of the case are described.
Mouse Mammary Tumor Virus Env–Derived Peptide Associates with Nucleolar Targets in Lymphoma, Mammary Carcinoma, and Human Breast Cancer
Authors: Allan Bar-Sinai, Nir Bassa, Maria Fischette, Michael M. Gottesman, Dona C. Love, John A. Hanover, Jacob Hochman
Journal: Cancer Research (2005)

Abstract We have previously shown that the leader peptide (p14) of the Env-precursor of mouse mammary tumor virus is translocated into the nucleoli of murine T cell lymphomas that harbor this virus. Using a polyclonal antibody against recombinant p14, we show here that p14 is also localized to the nucleoli of murine mammary carcinomas and some human breast cancer samples. Affinity purification studies define a number of proteins, mostly nucleolar, that bind p14. Taken together, these findings point towards a more general involvement of p14 in lymphomagenesis and mammary carcinogenesis.
The Role of the Host in the Chemotherapy of Tuberculosis
Authors: P. D. Hart
Journal: BMJ (1954)

Early ImprovementExperiment and experience of human tuberculosis show that acute recent disease is, to begin with, particularly re- sponsive to chemotherapy.Such acute forms of the disease indicate a relative failure of the host, due either to a low resistance or to an overwhel.mingdose of bacilli.From this it may be inferred that in some instances a low host resistance may actually favour chemotherapy, though this does not necessarily imply a greater overall benefit to the host.4891
Modeling the 3D structure of GPCRs from sequence
Authors: Sharon Shacham, Maya Topf, Noa Avisar, Fabian Glaser, Yael Marantz, Shay Bar‐Haim, Silvia Noiman, Zvi Naor, Oren M. Becker
Journal: Medicinal Research Reviews (2001)

Abstract G‐protein‐coupled receptors (GPCRs) are a large and functionally diverse protein superfamily, which form a seven transmembrane (TM) helices bundle with alternating extra‐cellular and intracellular loops. GPCRs are considered to be one of the most important groups of drug targets because they are involved in a broad range of body functions and processes and are related to major diseases. In this paper we present a new technology, named PREDICT, for modeling the 3D structure of any GPCR from its amino acid sequence. This approach takes into account both internal protein properties (i.e., the amino acid sequence) and the properties of the membrane environment. Unlike competing approaches, the new technology does not rely on the single known structure of rhodopsin, and is thus capable of predicting novel GPCR conformations. We demonstrate the capabilities of PREDICT in reproducing the known experimental structure of rhodopsin. In principle, PREDICT‐generated models offer new opportunities for structure‐based drug discovery towards GPCR targets. © 2001 John Wiley &amp; Sons, Inc. Med Res Rev, 21, No. 5, 472–483, 2001
Neuroregulators and Sleep Mechanisms
Authors: R B Holman, G R Elliott, J D Barchas
Journal: Annual Review of Medicine (1975)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Epidemiologic Study of In-Hospital Cardiopulmonary Resuscitation in the Elderly
Authors: William J. Ehlenbach, Amber E. Barnato, J. Randall Curtis, William Kreuter, Thomas D. Koepsell, Richard A. Deyo, Renee D. Stapleton
Journal: New England Journal of Medicine (2009)

It is unknown whether the rate of survival after in-hospital cardiopulmonary resuscitation (CPR) is improving and which characteristics of patients and hospitals predict survival.We examined fee-for-service Medicare data from 1992 through 2005 to identify beneficiaries 65 years of age or older who underwent CPR in U.S. hospitals. We examined temporal trends in the incidence of CPR and the rate of survival after CPR, as well as patient- and hospital-level predictors of survival to discharge.We identified 433,985 patients who underwent in-hospital CPR; 18.3% of these patients (95% confidence interval [CI], 18.2 to 18.5) survived to discharge. The rate of survival did not change substantially during the period from 1992 through 2005. The overall incidence of CPR was 2.73 events per 1000 admissions; the incidence was higher among black and other nonwhite patients. The proportion of patients undergoing in-hospital CPR before death increased over time and was higher for nonwhite patients. The survival rate was lower among patients who were men, were older, had more coexisting illnesses, or were admitted from a skilled-nursing facility. The adjusted odds of survival for black patients were 23.6% lower than those for similar white patients (95% CI, 21.2 to 25.9). The association between race and survival was partially explained by hospital effects: black patients were more likely to undergo CPR in hospitals that have lower rates of post-CPR survival. Among patients surviving in-hospital CPR, the proportion of patients discharged home rather than to a health care facility decreased over time.Survival after in-hospital CPR did not improve from 1992 through 2005. The proportion of in-hospital deaths preceded by CPR increased, whereas the proportion of survivors discharged home after undergoing CPR decreased. Black race was associated with higher rates of CPR but lower rates of survival after CPR.
Biochemistry of Altered Brain Proteins in Alzheimer's Disease
Authors: D J Selkoe
Journal: Annual Review of Neuroscience (1989)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Identification of the complement decay-accelerating factor (DAF) on epithelium and glandular cells and in body fluids.
Authors: M E Medof, E I Walter, J L Rutgers, D M Knowles, V Nussenzweig
Journal: The Journal of Experimental Medicine (1987)

Decay-accelerating factor (DAF) is a 70 kD membrane regulatory protein that prevents the activation of autologous complement on cell surfaces. Using immunohistochemical methods and a radioimmunometric assay based on mAbs to DAF, we found large amounts of membrane-associated DAF antigen on the epithelial surface of cornea, conjunctiva, oral and gastrointestinal mucosa, exocrine glands, renal tubules, ureter and bladder, cervical and uterine mucosa, and pleural, pericardial and synovial serosa. Additionally, we detected soluble DAF antigen in plasma, tears, saliva, and urine, as well as in synovial and cerebrospinal fluids. While plasma, tear, and saliva DAF are larger than erythrocyte (Ehu) membrane DAF by Western blot analysis, urine DAF is slightly smaller (67,000) in Mr. Unlike purified Ehu DAF, however, urine DAF is unable to incorporate into the membrane of red cells. Although its inhibitory activity on the complement enzyme C3-convertase is lower than that of Ehu DAF, it is comparable to that of serum C4 binding protein (C4bp). Biosynthetic studies using cultured foreskin epithelium and Hela cells disclosed DAF levels (approximately 2 X 10(5) molecules/cell) exceeding those on blood cells. In addition, these studies revealed the synthesis of two DAF species, one with apparent Mr corresponding to that of epithelial cell membrane DAF and the other to urine DAF, suggesting that the urine DAF variant arises from adjacent epithelium. The function of DAF in body fluids is unknown, but the observation that urine DAF has C4bp-(or factor H-)like activity shows that it could inhibit the fluid phase activation of the cascade.
Prospective derivation and validation of early dynamic model for predicting outcome in patients with acute liver failure
Authors: Ramesh Kumar, None Shalimar, Hanish Sharma, Rohit Goyal, Ajay Kumar, Shankar Khanal, Shyam Prakash, S Datta Gupta, Subrat Kumar Panda, Subrat Kumar Acharya
Journal: Gut (2012)

<h3>Objective</h3> It is difficult to predict the outcome in patients with acute liver failure (ALF) using existing prognostic models. This study investigated whether early changes in the levels of dynamic variables can predict outcome better than models based on static baseline variables. <h3>Design</h3> 380 patients with ALF (derivation cohort n=244, validation cohort n=136) participated in a prospective observational study. The derivation cohort was used to identify predictors of mortality. The ALF early dynamic (ALFED) model was constructed based on whether the levels of predictive variables remained persistently high or increased over 3 days above the discriminatory cut-off values identified in this study. The model had four variables: arterial ammonia, serum bilirubin, international normalised ratio and hepatic encephalopathy &gt;grade II. The model was validated in a cohort of 136 patients with ALF. <h3>Results</h3> The ALFED model demonstrated excellent discrimination with an area under the receiver operator characteristic curve of 0.91 in the derivation cohort and of 0.92 in the validation cohort. The model was well calibrated in both cohorts and showed a similar increase in mortality with increasing risk scores from 0 to 6. The performance of the ALFED model was superior to the King9s College Hospital criteria and the Model for End stage Liver Disease score, even when their 3-day serial values were taken into consideration. An ALFED score of ≥4 had a high positive predictive value (85%) and negative predictive value (87%) in the validation cohort. <h3>Conclusion</h3> The ALFED model accurately predicted outcome in patients with ALF, which may be useful in clinical decision-making.
PHYLOGENETIC ORIGINS OF ANTIBODY STRUCTURE
Authors: J. Marchalonis, G. M. Edelman
Journal: The Journal of Experimental Medicine (1966)

The anuran amphibian, Rana catesbiana, has been found to possess at least two kinds of immunoglobulins corresponding to γG- and γM-classes. These classes have the same chain structures as those of their counterparts in higher animal species. Light chains of both immunoglobulins had molecular weights of 20,000. Heavy chains of the γM-class had molecular weights of 72,100; those of the γG-class had molecular weights of 53,600. The carbohydrate content of the γG-immunoglobulin was 2.1%, and that of the γM-protein was 10.8%. The amino acid compositions of the immunoglobulins were generally similar to those of mammalian immunoglobulins. After a single injection of phage antigen (f2), the order of appearance of phage-neutralizing activity in the frog immunoglobulin classes was (a) γM-antibodies, and (b) γG-antibodies. The results of this and previous studies suggest that the γG-immunoglobulins emerged at some point in evolution between the elasmobranchs and the anuran amphibians.
Regression of Electrocardiographic Left Ventricular Hypertrophy and Decreased Incidence of New-Onset Atrial Fibrillation in Patients With Hypertension
Authors: Peter M Okin, Kristian Wachtell, Richard B Devereux, Katherine E Harris, Sverker Jern, Sverre E Kjeldsen, Stevo Julius, Lars H Lindholm, Markku S Nieminen, Jonathan M Edelman, Darcy A Hille, Björn Dahlöf
Journal: JAMA (2006)

Atrial fibrillation (AF) is associated with increased risk of mortality and cardiovascular events, particularly stroke, making prevention of new-onset AF a clinical priority. Although the presence and severity of electrocardiographic left ventricular hypertrophy (LVH) appear to predict development of AF, whether regression of electrocardiographic LVH is associated with a decreased incidence of AF is unclear.To test the hypothesis that in-treatment regression or continued absence of electrocardiographic LVH during antihypertensive therapy is associated with a decreased incidence of AF, independent of blood pressure and treatment modality.Double-blind, randomized, parallel-group study conducted in 1995-2001 among 8831 men and women with hypertension, aged 55-80 years (median, 67 years), with electrocardiographic LVH by Cornell voltage-duration product or Sokolow-Lyon voltage, with no history of AF, without AF on the baseline electrocardiogram, and enrolled in the Losartan Intervention for Endpoint Reduction in Hypertension Study.Losartan- or atenolol-based treatment regimens, with follow-up assessments at 6 months and then yearly until death or study end.New-onset AF in relation to electrocardiographic LVH determined at baseline and subsequently. Electrocardiographic LVH was measured using sex-adjusted Cornell product criteria ({R(aVL) + S(V3) [+ 6 mm in women]} x QRS duration).After a mean (SD) follow-up of 4.7 (1.1) years, new-onset AF occurred in 290 patients with in-treatment regression or continued absence of Cornell product LVH for a rate of 14.9 per 1000 patient-years and in 411 patients with in-treatment persistence or development of LVH by Cornell product criteria for a rate of 19.0 per 1000 patient-years. In time-dependent Cox analyses adjusted for treatment effects, baseline differences in risk factors for AF, baseline and in-treatment blood pressure, and baseline severity of electrocardiographic LVH, lower in-treatment Cornell product LVH treated as a time-varying covariate was associated with a 12.4% lower rate of new-onset AF (adjusted hazard ratio [HR], 0.88; 95% CI, 0.80-0.97; P = .007) for every 1050 mm x msec (per 1-SD) lower Cornell product, with persistence of the benefit of losartan vs atenolol therapy on developing AF (HR, 0.83; 95% CI, 0.71-0.97; P = .01).Lower Cornell product electrocardiographic LVH during antihypertensive therapy is associated with a lower likelihood of new-onset AF, independent of blood pressure lowering and treatment modality in essential hypertension. These findings suggest that antihypertensive therapy targeted at regression or prevention of electrocardiographic LVH may reduce the incidence of new-onset AF.
Additive Beneficial Effects of Fenofibrate Combined With Atorvastatin in the Treatment of Combined Hyperlipidemia
Authors: Kwang Kon Koh, Michael J. Quon, Seung Hwan Han, Wook-Jin Chung, Jeong Yeal Ahn, Yiel-Hea Seo, In Suck Choi, Eak Kyun Shin
Journal: Journal of the American College of Cardiology (2005)
Sodium cromoglycate and atropine block the fall in FEV1 but not the cough induced by hypotonic mist.
Authors: R W Fuller, J G Collier
Journal: Thorax (1984)

In a group of patients with mild asthma the inhalation of mist derived from ultrasonically nebulised distilled water caused an increase in cough and a fall in FEV1. Double blind administration for five minutes of sodium cromoglycate (from an original solution containing 30 mg/ml) or atropine (2 mg/ml) by inhalation from a Minineb nebuliser, 30 minutes before the mist challenge, caused a significant reduction in the fall in FEV1 (p less than 0.05), but not in cough, by comparison with the protection afforded by placebo (saline). In a second study the fall in FEV1 caused by the inhalation of distilled water was not significantly different from that seen in response to hypotonic sodium chloride (1.7 g/l, 58 mmol/l), but both produced a significantly greater fall than did a similar mist containing sodium cromoglycate at an original concentration of 10 mg/ml (58 mmol/l). The results show that both atropine and sodium cromoglycate can block the fall in FEV1 due to mist and that protection by sodium cromoglycate is immediate. These results suggest that sodium cromoglycate blocks the nervous reflexes concerned in the response to mist, probably in the afferent limb of the reflex.
Pollen deposition in intrathoracic airways
Authors: MN Driessen, PH Quanjer
Journal: European Respiratory Journal (1991)

The pathophysiological mechanisms of pollen-induced asthma have until now remained unclear, because pollen particles have generally been considered too large to penetrate into the lower respiratory tract. Such grains are therefore believed to be unable to induce an immunological response in the lower respiratory tract. There is evidence, however, that a small percentage of large particles (20-30 microns) may penetrate into the peripheral areas of the lung. It also appears that small airborne units of less than 5 microns with the same antigenic activity as pollen, may contribute to inhaled allergen burdens. Pollen asthma probably results from a gradual cumulative effect of deposition of small amounts of allergen in lower airways, and is hence poorly correlated with daily pollen counts.
Enhanced antilymphoma efficacy of CD19-redirected influenza MP1–specific CTLs by cotransfer of T cells modified to present influenza MP1
Authors: Laurence J. N. Cooper, Zaid Al-Kadhimi, Lisa Marie Serrano, Timothy Pfeiffer, Simon Olivares, Adrian Castro, Wen-Chung Chang, Sergio Gonzalez, David Smith, Stephen J. Forman, Michael C. Jensen
Journal: Blood (2004)
Essential role of macrophage colony-stimulating factor in the osteoclast differentiation supported by stromal cells.
Authors: H Kodama, M Nose, S Niida, A Yamasaki
Journal: The Journal of Experimental Medicine (1991)

Severe deficiency of osteoclasts, monocytes, and peritoneal macrophages in osteopetrotic (op/op) mutant mice is caused by the absence of functional macrophage colony-stimulating factor (M-CSF). To clarify the role of M-CSF in the osteoclast differentiation, we established a clonal stromal cell line OP6L7 capable of supporting hemopoiesis from newborn op/op mouse calvaria. Although very few macrophages appeared in the cocultures of bone marrow cells and OP6L7 cells, a 50-fold larger number of macrophages was detected in the day 7 cocultures when purified recombinant human M-CSF (rhM-CSF) was exogenously supplied. Tartrate-resistant acid phosphatase (TRACP; a marker enzyme of osteoclasts)-positive cells appeared only when bone marrow cells were cultured in contact with OP6L7 cells and both rhM-CSF and 1 alpha, 25 (OH)2D3 were added. The TRACP-positive cells became multinucleated with increasing time in culture and expressed the c-fms/M-CSF receptor. These results indicate that both contact with stromal cells and M-CSF are requisite for osteoclast differentiation under physiological conditions.
Vascular Reactivity and Flow Characteristics of Radial Artery and Long Saphenous Vein Coronary Bypass Grafts
Authors: Carolyn M. Webb, Neil E. Moat, Chee F. Chong, Peter Collins
Journal: Circulation (2010)

Radial artery (RA) aortocoronary bypass grafts anastomosed to a branch of the circumflex coronary artery have significantly better patency rates than saphenous vein (SV) grafts at 5 years, but the physiological characteristics and mechanisms involved are not clearly defined. We compared RA and SV graft vasomotor and flow responses to endothelium-dependent and -independent stimuli 5 years after surgery in a subgroup of patients enrolled in the Radial artery versus Saphenous Vein Patency (RSVP) trial.Twenty-seven patients were included in the study (RA, n=15; SV, n=12). Graft blood flow was calculated from flow velocity, measured by intracoronary Doppler, and luminal diameter, measured by quantitative coronary angiography, before and after intragraft infusions of adenosine, acetylcholine, and isosorbide dinitrate. At rest, RA luminal diameters were significantly smaller than SV luminal diameters (P=0.029), blood flow velocity was greater in RA than SV (P=0.008), and volume blood flows were similar. RA but not SV dilated in response to adenosine and isosorbide dinitrate (all P<0.05, RA versus SV, percent change from baseline), and there were no significant differences in the diameter responses to acetylcholine. Volume blood flow responses to adenosine, acetylcholine, and isosorbide dinitrate were comparable.Five years after surgery, RA coronary bypass conduits grafted to a single coronary territory demonstrated preserved flow-mediated vasodilatation, whereas SV grafts did not. Our results may provide insight into the more favorable patency of RA grafts over SV grafts.http://www.clinicaltrials.gov. Unique identifier: NCT00139399.