tbuckley/cabot-search huggingface dataset:
Antiangiogenic activity of the selective cyclooxygenase 2 inhibitor rofecoxib in human colorectal cancer liver metastases
Authors: C R Chalmers
Journal: Gut (2006)

We have previously reported that colorectal cancer (CRC) liver metastases from patients, who had received the selective cyclooxygenase 2 (COX-2) inhibitor rofecoxib (Vioxx) 25 mg daily for a mean period of 26 days, had a 31% lower mean microvessel density compared with tumours from individuals who had received placebo only.1 These data suggest that one mechanism of action of rofecoxib in human CRC liver metastases might be inhibition of angiogenesis. Therefore, we investigated the potential antiangiogenic activity of rofecoxib in human CRC liver metastases by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI), before and after treatment with oral rofecoxib 25 mg daily for 28 days. As short term treatment of rats with the selective COX-2 inhibitor celecoxib is associated with an increase in serum levels of the endogenous antiangiogenic factor endostatin,2 we also measured serum levels of endostatin and the proangiogenic factor vascular endothelial growth factor (VEGF), at the same time as DCE-MRI.

Patients undergoing liver resection of CRC liver metastases were enrolled if diagnostic MRI identified a single metastasis greater than 1.5 cm …
Role of the Urokinase Plasminogen Activator Receptor in Mediating Impaired Efferocytosis of Anti-SSA/Ro–Bound Apoptotic Cardiocytes
Authors: Paraskevi Briassouli, Elena V. Komissarova, Robert M. Clancy, Jill P. Buyon
Journal: Circulation Research (2010)

Binding of maternal anti-Ro/La antibodies to cognate antigen expressed on apoptotic cardiocytes decreases clearance by healthy cardiocytes, which may contribute to the development of autoimmune associated congenital heart block and fatal cardiomyopathy.
Aid agency pledges to carry on in Afghanistan despite medical workers' deaths
Authors: A. O'Dowd
Journal: BMJ (2010)

An aid agency working in Afghanistan has vowed to carry on its operations despite the murders of 10 of its volunteers, including the British doctor Karen Woo, last week.

But it is feared that the incident could deter the further recruitment of volunteers.

Dr Woo, aged 36, was shot on 5 August along with nine other volunteers―six Americans, among whom were an optometrist, a nurse, and a dentist; one German; and two Afghan interpreters―working for the humanitarian aid agency International Assistance Mission (IAM) in Afghanistan.

The members of the group, known as the Nuristan eye camp team, were killed in an ambush in the northeastern Badakhshan province after returning from delivering medical supplies and care to people living in mountain communities as part of the …
EMD 53998 sensitizes the contractile proteins to calcium in intact ferret ventricular muscle.
Authors: J A Lee, D G Allen
Journal: Circulation Research (1991)

EMD 53998 (a thiadiazinone) is an inotropic drug that produces a pronounced increase in the Ca2+ sensitivity of the contractile proteins in skinned cardiac fibers. The present study was undertaken to determine whether this effect on Ca2+ sensitivity could explain the increase in tension observed in intact ventricular muscle. The experiments were performed on isolated ferret papillary muscles that had been microinjected with aequorin to measure the intracellular Ca2+ concentration. Force and intracellular Ca2+ concentration were monitored before, during, and after application of EMD 53998. EMD 53998 (5 microM) increased developed tension by 230%; aequorin light transients increased by only 85%, and this increase was reduced and became insignificant in the presence of agents that prevent catecholamine release. When a similar increase in developed tension was produced by elevation of extracellular calcium, the aequorin light transients increased by 240%. Thus, EMD 53998 produces a substantial Ca2+ sensitization in intact ventricular muscle, and this can explain most of its inotropic effect. In addition, EMD 53998 caused a small prolongation of the time course of contraction and a small reduction of the time course of the aequorin light transient. A computer model is described that shows that both these effects can be explained by the effect of EMD 53998 on Ca2+ sensitivity. At much higher concentrations, EMD 53998 also caused an increase in resting tension. EMD 53998 is the first agent for which much of the inotropic effect in intact cardiac muscle can be accounted for by increased Ca2+ sensitivity of the contractile proteins. Inotropic agents with this mechanism of action cause increased force production with much less increase in the intracellular Ca2+ transients than conventional agents and, therefore, increase the energy efficiency of the myocardium and are less likely to cause Ca(2+)-activated arrhythmias.
Neutrophilic inflammation: "Don't you go to pieces on me!"
Authors: R. A. Stockley
Journal: European Respiratory Journal (2006)

eutrophilic infiltration is a phenomenon observed even in the healthy lung.However, increased infiltration occurs in many acute and chronic lung diseases and although necessary as part of the lung's secondary defence systems, infiltration has been implicated in pathogenic processes leading to the tissue damage associated with many diseases.Not only do the neutrophil contents possess the ability to damage tissues, they may also generate chemotactic factors with the potential to amplify leukocyte infiltration [1][2][3].
AGGLUTINATION AFFINITIES OF THE ABORTUS-MELITENSIS GROUP OF BACTERIA WITH SPECIAL REFERENCE TO TWO HUMAN STRAINS
Authors: Marion L. Orcutt
Journal: The Journal of Experimental Medicine (1926)

The conclusions to be drawn from this study are that while there appears to be evidence of serological distinctions between B. abortus and B. melitensis cultures as studied by earlier workers, the experiments reported in this paper show no serological distinctions among the six strains used in the study. B. melitensis II and B. melitensis III were found to be identical with the bovine and swine strains by means of agglutination and agglutinin absorption reactions in unheated sera, by agglutination in heated sera, and with the use of heated cultures in unheated and heated sera.
Penetratin Improves Tumor Retention of Single-Chain Antibodies: A Novel Step toward Optimization of Radioimmunotherapy of Solid Tumors
Authors: Maneesh Jain, Subhash C. Chauhan, Ajay P. Singh, Ganesh Venkatraman, David Colcher, Surinder K. Batra
Journal: Cancer Research (2005)

Abstract Single-chain Fv (scFv) antibody fragments exhibit improved pharmacokinetics and biodistribution compared with intact IgG. The tumor uptake of scFvs is rapid, and the serum half-life is shorter than IgG. However, scFvs exhibit lower net dose deposition in the tumor due to a shorter residence time that limits their use in radioimmunotherapy. To improve the tumor uptake and retention of scFvs, we investigated the utility of cell-penetrating peptides, penetratin and transactivator of transcription (TAT). Biodistribution studies were done in LS174T tumor-bearing mice with divalent scFv derived from anti–tumor-associated glycoprotein 72 monoclonal antibody (mAb) CC49. Penetratin increased the tumor retention of scFvs without affecting the peak dose accumulation. The percentage of doses retained in tumors at 24 hours postadministration with a control (no peptide), penetratin, and TAT were 27.25%, 79.84%, and 48.55%, respectively, of that accumulated at 8 hours postinjection. The tumor-to-blood ratios at 24 hours postadministration were 7.14, 19.53, and 16.48 with control, penetratin, and TAT treatment, respectively, whereas the pharmacokinetics were unaltered. Coinjection with TAT, however, resulted in increased uptake of the radioconjugate by the lungs. Autoradiography of the excised tumors indicated a more homogenous distribution of the radiolabeled scFv with both penetratin and TAT in comparison with the control treatment. Real-time whole-body imaging of the live animals confirmed improved tumor localization with penetratin without any increase in the uptake by normal tissues. In conclusion, a significant improvement in the tumor retention of sc(Fv)2 was achieved by administration of penetratin. Therefore, the combination of penetratin and scFvs has the potential of improving the utility of mAb-based radiopharmaceuticals.
Nucleases and Adenosine 3′,5′-Cyclic Monophosphate Phosphodiesterase Activities in Murine Sarcoma Virus (Moloney)-Infected Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: K C Tsou, K W Lo, R B Herberman
Journal: JNCI Journal of the National Cancer Institute (1978)

To provide information on the role of nucleases in oncogenic virus infection, the activities of 3'-nucleotide phosphodiesterase (3'-NPDase), 5'-nucleotide phosphodiesterase (5'-NPDase), acid deoxyribonuclease (DNase II), and 3',5'-cyclic AMP phosphodiesterase (cAMPDase) in spleen extracts of murine sarcoma virus-infected C57BL/6 inbred mice were studied. At the peak of tumor growth and of the cell-mediated cytotoxic response (CMC) against tumor-associated antigens, 3'-NPDase, 5'-NPDase, and DNase II all showed depressed activities in the spleen, whereas the activity of cAMPDase in the spleen increased at the peak of CMC and remained elevated thereafter. Serum enzyme activities of the infected mice were also determined, and only 3'-NPD-ase in serum correlated well with CMC. Inasmuch as the correlation of the tumor growth with CMC was established in this system, further study on tumors with variance between CMC and growth is necessary to determine if serum 3'-NPDase is a useful biochemical marker for CMC in vivo.
Does vasectomy accelerate testicular tumour? Importance of testicular examinations before and after vasectomy.
Authors: A R Cale, M Farouk, R J Prescott, I W Wallace
Journal: BMJ (1990)

An association between vasectomy and the development of testicular tumors, and the importance of testicular examinations both before and after a vasectomy is discussed. Patients diagnosed with testicular tumors within the last ten years were examined at Bangour General Hospital in Scotland. From 1977-87, 37 patients under age 60 were detected with testicular tumors. 3079 men underwent a vasectomy during this time. 8 were diagnosed with the tumors. Average time between the vasectomy and the diagnosis of the tumors was 1-9 years. The number of cases in men aged 20-59, and the age specific incidence were calculated from population on figures. Incidences of tumors, combined with the number of patient years of risk contained in the group who underwent a vasectomy, were used to ascertain the expected number of tumors in the 1-9 year group. Observed number was 8. As result, the ratio for patients with a vasectomy was 4.2 (95% confidence interval 1.8 to 8.2) with absolute annual incidence of testicular tumor in men who had had a vasectomy at 53/100000 men. Further suggested is that vasectomy accelerates the incidence of a palpable tumor from a carcinoma in situ, or possibly that tumors are often overlooked during a vasectomy. An examination before a vasectomy should detect palpable tumors, with carcinomas being detected by cytological examination of semen. Men should be screened by examination 12-18 months after a vasectomy. In light of the growing popularity of vasectomy as a more accepted means of contraception, how vasectomy affects the etiology of testicular malignancy is an important issue.
Acute Toxicity and Compliance with Tomotherapy Based Adjuvant Intensity Modulated Radiotherapy in Patients with Gastric Cancer: Results From Prospective Study
Authors: Supriya Chopra, Aditi Agarwal, Reena Engineer, Siji Paul, Biji Thomas, Shaesta Mehta, Prachi Patil, Shailesh Shrikhande, Mahesh Goel, Shyam Shrivastava
Journal: Annals of Oncology (2013)
Phase I trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem glioma
Authors: Daphne A. Haas-Kogan, Anuradha Banerjee, Mehmet Kocak, Michael D. Prados, J. Russell Geyer, Maryam Fouladi, Tracy McKnight, Tina Young Poussaint, Alberto Broniscer, Susan M. Blaney, James M. Boyett, Larry E. Kun
Journal: Neuro-Oncology (2008)

The purpose of this study is to estimate the maximum-tolerated dose (MTD) and describe toxicities and preliminary clinical effects of tipifarnib, a farnesyltransferase (FTase) inhibitor, administered concurrently with radiation therapy in children with newly diagnosed intrinsic diffuse brainstem glioma (BSG). Children >or=3 and <or=21 years of age with newly diagnosed nondisseminated intrinsic diffuse BSG were treated with concurrent tipifarnib and radiation, followed by adjuvant tipifarnib. Escalating doses of tipifarnib were administered orally twice daily, continuously, for the entire duration of radiation, followed by a 2-week break. Postradiation tipifarnib, 200 mg/m(2)/dose, was administered twice daily for 21 consecutive days, in 28-day cycles. Seventeen patients, median age 5.9 years (range, 3.6-13.8), received external beam radiation therapy administered concurrently with tipifarnib at dose levels ranging from 100 to 150 mg/m(2)/dose, followed by adjuvant tipifarnib for up to 24 months in the absence of tumor progression or unacceptable toxicity. Dose-limiting toxicities were grade 3 skin rash in one patient at the 125 mg/m(2) dose level and two patients at the 150 mg/m(2) dose level, and grade 3 pneumonia with a normal absolute neutrophil count (ANC) in one patient at the 150 mg/m(2) dose level. One patient had isolated grade 4 neutropenia at the 150 mg/m(2) dose level. The MTD of tipifarnib administered was estimated as 125 mg/m(2)/dose b.i.d. When administered concurrently with radiation, the dose-limiting toxicities of tipifarnib are rash, infection with normal ANC, and neutropenia. The MTD of tipifarnib with concurrent radiation is 125 mg/m(2)/dose b.i.d. One-year survival and progression-free survival estimates are 36.4% (SE 16.7%) and 9.4% (SE 6.3%), respectively.
NATURE OF THE STIMULATING CELL IN THE SYNGENEIC AND THE ALLOGENEIC MIXED LYMPHOCYTE REACTION IN MICE
Authors: H. von Boehmer, K. Shortman, Ann P. Adams
Journal: The Journal of Experimental Medicine (1972)

Thymus cells from CBA and BALB/c mice are stimulated by syngeneic peripheral lymphoid cells in a "one-way" mixed lymphocyte reaction. The stimulating cell appears to be a mature B cell. Spleen cells from neonatal mice and thymus cells or bone marrow cells from adult mice are not able to induce DNA synthesis in syngeneic thymus cells, although they stimulate significantly allogeneic thymocytes. The ability of peripheral B cells to serve as stimulating cell in a syngeneic reaction develops with the age of the animal. The marginal stimulation of syngeneic thymus cells when 90% pure peripheral T cells were used as stimulating cells indicated that T cells alone were ineffective in stimulating in syngeneic mixed lymphocyte reaction. However they stimulated effective allogeneic thymocytes. On a cell-to-cell basis, light density splenic lymphocytes stimulated both syngeneic and allogeneic thymocytes better than did more dense lymphocytes. The data obtained suggest that stimuli other than those responsible for allogeneic stimulation induce proliferation of syngeneic thymus cells under identical culture conditions.
Why Physicians Favored Lipitor Over Simvastatin—Reply
Authors: Brian K. Alldredge, Steven R. Kayser
Journal: JAMA Internal Medicine (2013)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
The CAM-S: Development and Validation of a New Scoring System for Delirium Severity in 2 Cohorts
Authors: Sharon K. Inouye, Cyrus M. Kosar, Douglas Tommet, Eva M. Schmitt, Margaret R. Puelle, Jane S. Saczynski, Edward R. Marcantonio, Richard N. Jones
Journal: Annals of Internal Medicine (2014)

Quantifying the severity of delirium is essential to advancing clinical care by improved understanding of delirium effect, prognosis, pathophysiology, and response to treatment. To develop and validate a new delirium severity measure (CAM-S) based on the Confusion Assessment Method. Validation analysis in 2 independent cohorts. Three academic medical centers. The first cohort included 300 patients aged 70 years or older scheduled for major surgery. The second included 919 medical patients aged 70 years or older. A 4-item short form and a 10-item long form were developed. Association of the maximum CAM-S score during hospitalization with hospital and posthospital outcomes related to delirium was evaluated. Representative results included adjusted mean length of stay, which increased across levels of short-form severity from 6.5 days (95% CI, 6.2 to 6.9 days) to 12.7 days (CI, 11.2 to 14.3 days) (P for trend &lt; 0.001) and across levels of long-form severity from 5.6 days (CI, 5.1 to 6.1 days) to 11.9 days (CI, 10.8 to 12.9 days) (P for trend &lt; 0.001). Representative results for the composite outcome of adjusted relative risk of death or nursing home residence at 90 days increased progressively across levels of short-form severity from 1.0 (referent) to 2.5 (CI, 1.9 to 3.3) (P for trend &lt; 0.001) and across levels of long-form severity from 1.0 (referent) to 2.5 (CI, 1.6 to 3.7) (P for trend &lt; 0.001). Data on clinical outcomes were measured in an older data set limited to patients aged 70 years or older. The CAM-S provides a new delirium severity measure with strong psychometric properties and strong associations with important clinical outcomes. National Institute on Aging.
K <sup>+</sup> Channel Blockers Inhibit Tissue Factor Expression by Human Monocytic Cells
Authors: David J. Crutchley, Lobella B. Conanan, Benito G. Que
Journal: Circulation Research (1995)

Abstract Human monocytes express the important procoagulant protein, tissue factor (TF), after stimulation by a variety of agents, including bacterial lipopolysaccharide (LPS). Monocyte TF expression may contribute to intravascular coagulation in a number of disease states. The present studies show that monocytic cell TF expression can be inhibited by several agents known to block cellular K + channels. Exposure of human peripheral blood to 100 ng/mL LPS for 2 hours led to pronounced TF procoagulant activity associated with the mononuclear cell fraction. This was inhibited by 4-aminopyridine (2 mmol/L), tetraethylammonium chloride (10 mmol/L), and apamin (1 μmol/L). In contrast, charybdotoxin (100 nmol/L) was inactive. More detailed studies were carried out in cultured human monocytic tumor THP-1 cells. These cells exhibited low but detectable levels of TF mRNA, measured by reverse transcription and polymerase chain reaction; cell surface procoagulant activity, measured by a plasma clotting assay; and cell homogenate TF antigen, measured by immunoassay. Exposure of THP-1 cells to 1 μg/mL LPS led to threefold to fivefold increases in all three parameters. Basal and LPS-induced levels of all three parameters were reduced in a dose-dependent manner by 4-aminopyridine (I 50 , 1 mmol/L) and tetraethylammonium chloride (I 50 , 20 mmol/L) but not by apamin or charybdotoxin. Expression of TF activity was also inhibited by glibenclamide, an inhibitor of ATP-dependent K + channels (I 50 , 25 μmol/L). These results suggest that facilitation of TF synthesis may be an important role for K + channels in monocytes.
Injectable Self-Assembling Peptide Nanofibers Create Intramyocardial Microenvironments for Endothelial Cells
Authors: Michael E. Davis, J.P. Michael Motion, Daria A. Narmoneva, Tomosaburo Takahashi, Daihiko Hakuno, Roger D. Kamm, Shuguang Zhang, Richard T. Lee
Journal: Circulation (2005)

Background— Promoting survival of transplanted cells or endogenous precursors is an important goal. We hypothesized that a novel approach to promote vascularization would be to create injectable microenvironments within the myocardium that recruit endothelial cells and promote their survival and organization. Methods and Results— In this study we demonstrate that self-assembling peptides can be injected and that the resulting nanofiber microenvironments are readily detectable within the myocardium. Furthermore, the self-assembling peptide nanofiber microenvironments recruit progenitor cells that express endothelial markers, as determined by staining with isolectin and for the endothelial-specific protein platelet–endothelial cell adhesion molecule-1. Vascular smooth muscle cells are recruited to the microenvironment and appear to form functional vascular structures. After the endothelial cell population, cells that express α-sarcomeric actin and the transcription factor Nkx2.5 infiltrate the peptide microenvironment. When exogenous donor green fluorescent protein–positive neonatal cardiomyocytes were injected with the self-assembling peptides, transplanted cardiomyocytes in the peptide microenvironment survived and also augmented endogenous cell recruitment. Conclusions— These experiments demonstrate that self-assembling peptides can create nanofiber microenvironments in the myocardium and that these microenvironments promote vascular cell recruitment. Because these peptide nanofibers may be modified in a variety of ways, this approach may enable injectable tissue regeneration strategies.
Autocrine VEGF–VEGFR2–Neuropilin-1 signaling promotes glioma stem-like cell viability and tumor growth
Authors: Petra Hamerlik, Justin D. Lathia, Rikke Rasmussen, Qiulian Wu, Jirina Bartkova, MyungHee Lee, Pavel Moudry, Jiri Bartek, Walter Fischer, Jiri Lukas, Jeremy N. Rich, Jiri Bartek
Journal: The Journal of Experimental Medicine (2012)

Although vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) is traditionally regarded as an endothelial cell protein, evidence suggests that VEGFRs may be expressed by cancer cells. Glioblastoma multiforme (GBM) is a lethal cancer characterized by florid vascularization and aberrantly elevated VEGF. Antiangiogenic therapy with the humanized VEGF antibody bevacizumab reduces GBM tumor growth; however, the clinical benefits are transient and invariably followed by tumor recurrence. In this study, we show that VEGFR2 is preferentially expressed on the cell surface of the CD133+ human glioma stem-like cells (GSCs), whose viability, self-renewal, and tumorigenicity rely, at least in part, on signaling through the VEGF-VEGFR2–Neuropilin-1 (NRP1) axis. We find that the limited impact of bevacizumab-mediated VEGF blockage may reflect ongoing autocrine signaling through VEGF–VEGFR2–NRP1, which is associated with VEGFR2–NRP1 recycling and a pool of active VEGFR2 within a cytosolic compartment of a subset of human GBM cells. Whereas bevacizumab failed to inhibit prosurvival effects of VEGFR2-mediated signaling, GSC viability under unperturbed or radiation-evoked stress conditions was attenuated by direct inhibition of VEGFR2 tyrosine kinase activity and/or shRNA-mediated knockdown of VEGFR2 or NRP1. We propose that direct inhibition of VEGFR2 kinase may block the highly dynamic VEGF–VEGFR2–NRP1 pathway and inspire a GBM treatment strategy to complement the currently prevalent ligand neutralization approach.