tbuckley/cabot-search huggingface dataset:
Foxing Smooth Muscle Cells
Authors: Trevor D. Littlewood, Martin R. Bennett
Journal: Circulation Research (2007)

V ascular smooth muscle cells (VSMCs) are essential for the structural integrity and contractile responses of the arterial vessel wall.VSMC proliferation and survival are also implicated in vascular disease including restenosis following angioplasty or stenting, and VSMC apoptosis is an important regulator of plaque stability.Thus, unraveling the molecular mechanisms that govern the survival, proliferation and migration of VSMCs is of great clinical importance.In this issue of Circulation Research Lee et al 1 have added another piece to this jigsaw puzzle.They show that the rapid increase in expression of the secreted cysteine-rich angiogenic protein CYR61 following stimulation of VSMCs with either serum growth factors or angiotensin II in vitro, or after mechanical arterial injury in vivo, can be attenuated by FOXO3a.Previous studies have shown that CYR61 is highly expressed in human atherosclerotic plaques, correlating with the degree of stenosis and plaque histopathology. 2Lee et al 1 investigated how expression of CYR61 is regulated.The CYR61 promoter contains multiple binding sites for different transcriptional regulators.In particular, Lee et al 1 identified a site for Forkhead/winged helix box gene, group O (FOXO) family of transcription factors.Because previous studies had indicated that FOXO3a inhibits neointimal hyperplasia by promoting cell cycle arrest and apoptosis, 3,4 Lee et al 1 investigated whether FOXO3a influenced the expression of CYR61.They demonstrate that FOXO3a functions as a transcriptional repressor of CYR61.Because the serine/threonine kinase Akt/PKB phosphorylates and inhibits FOXO3a activity, Lee et al 1 used a modified allele that contains mutated Akt phosphorylation sites (TM-FOXO3a).Adenovirus-mediated expression of this constitutively active TM-FOXO3a protein in rat VSMCs represses both basal CYR61 expression and expression induced by serum or angiotensin II.This repression seems to be a direct effect because FOXO3a is detected at the CYR61 promoter by chromatin immunoprecipitation (ChIP).Moreover, a reporter assay shows that deletion of the FOXO binding site in the CYR61 promoter abrogates the repression of CYR61 expression by TM-FOXO3a.The kinetics of phosphorylation of
Glycoprotein Coat of the TA&lt;sub&gt;3&lt;/sub&gt; Cell. I. Removal of Carbohydrate and Protein Material From Viable Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: John F. Codington, Barbara H. Sanford, Roger W. Jeanloz
Journal: JNCI Journal of the National Cancer Institute (1970)

Incubation of viable TA3 ascites cells of the strain A mouse with neuraminidase released 0.44 mg of sialic acid per 109 cells, but no detectable protein in addition to that released in the absence of enzyme. This suggests that the reduced transplantability of the cells, after neuraminidase treatment, in the allogeneic C3H mouse is not due to the removal of nonspecific proteins from antigenic sites at the cell surface. Several methods for removing sialoglycopeptides, while maintaining cell viability, were studied. TPCK-trypsin or Pronase liberated carbohydrate and protein material weighing up to 15% of the dry weight of the cells and containing 71–74% of total cellular sialic acid. Ethylenediamine-tetraacetate released up to 11% of the cell weight, but less than 16% of the total sialic acid. Citrate was ineffective. All samples contained the same major carbohydrate components, mannose, galactose, glucose, N-acetylgalactosamine, Nacetylglucosamine, and sialic acid, but differed in the proportion of both carbohydrate and amino acid components. Successive trypsinizations of cells for short periods initially removed materials having high concentrations of sialic acid, hexosamine, and galactose. The sialic acid released by neuraminidase was composed of about 10% N-glycolylneuraminic acid and 90% N-acetylneuraminic acid.
PROGNOSTIC STUDIES IN MENTAL DISORDER
Authors: ARTHUR J. ROBINS
Journal: American Journal of Psychiatry (1954)

The methodology of a number of prognostic studies has been critically considered, with only incidental reference to the substantive content. The latter has validity only when principles of the scientific method have been applied in deriving and evaluating data. The extensive literature on psychological tests used in prognosis has not been reviewed, since that already has been done by Windle(32). Most of the research has been found to be so deficient in the use of research procedures as to place in doubt any of the findings. Together with the prognostic statements of the didactic literature, much of the content is of value chiefly because of the conceptual framework and the suggestions they provide of factors whose prognostic relevance should be investigated. These factors have appeared so often in the literature that it seems that sheer force of repetition may have given them an importance not always demonstrated by the specific research reviewed. Definitive research will be facilitated by a greater degree of interdisciplinary planning. The narrow orientation of particular investigators may have been reflected in the fact that definitions so frequently were not clarified, indicating perhaps the investigator's assumption that no other point of view existed. Little attention, for example, has been paid to contingency factors such as the association of particular furlough situations with outcome. Full coverage of biogenic, psychogenic, and sociogenic factors demands that research psychiatrists join forces with other social scientists, some of whom have been working for years on a related problem, the prediction of recidivism (21). Research design must be refined. The population must be identified, the sampling process indicated, and the criterion groups defined. All variables under study should be objectively described. Obtaining reliable and valid measures of factors is perhaps a greater problem than the analysis of these measures. Conclusions should be statistically evaluated for significance, and it should be recognized that generalizations apply only to the population sampled. In general, enough information should be reported so that replication would be possible. Prognostic research, which may involve establishing contact with a mobile group of former patients, is expensive. To produce results worth the cost in time and money, strict adherence to scientific procedure is necessary.
Synthesis and biologic properties of hydrophilic sapphyrins, a new class of tumor-selective inhibitors of gene expression
Authors: Zhong Wang, Philip S Lecane, Patricia Thiemann, Qing Fan, Cecilia Cortez, Xuan Ma, Danielle Tonev, Dale Miles, Louie Naumovski, Richard A Miller, Darren Magda, Dong-Gyu Cho, Jonathan L Sessler, Brian L Pike, Samantha M Yeligar, Mazen W Karaman, Joseph G Hacia
Journal: Molecular Cancer (2007)

Abstract Background Sapphyrin analogues and related porphyrin-like species have attracted attention as anticancer agents due to their selective localization in various cancers, including hematologic malignancies, relative to surrounding tissues. Sapphyrins are electron affinic compounds that generate high yields of singlet oxygen formation. Although initially explored in the context of photodynamic therapy, sapphyrins have intrinsic anticancer activity that is independent of their photosensitizing properties. However, the mechanisms for their anticancer activity have not been fully elucidated. Results We have prepared a series of hydrophilic sapphyrins and evaluated their effect on proliferation, uptake, and cell death in adherent human lung (A549) and prostate (PC3) cancer cell lines and in an A549 xenograft tumor model. PCI-2050, the sapphyrin derivative with the highest in vitro growth inhibitory activity, significantly lowered 5-bromo-2'-deoxyuridine incorporation in S-phase A549 cells by 60% within eight hours and increased levels of reactive oxygen species within four hours. The growth inhibition pattern of PCI-2050 in the National Cancer Institute 60 cell line screen correlated most closely using the COMPARE algorithm with known transcriptional or translational inhibitors. Gene expression analyses conducted on A549 plateau phase cultures treated with PCI-2050 uncovered wide-spread decreases in mRNA levels, which especially affected short-lived transcripts. Intriguingly, PCI-2050 increased the levels of transcripts involved in RNA processing and trafficking, transcriptional regulation, and chromatin remodeling. We propose that these changes reflect the activation of cellular processes aimed at countering the observed wide-spread reductions in transcript levels. In our A549 xenograft model, the two lead compounds, PCI-2050 and PCI-2022, showed similar tumor distributions despite differences in plasma and kidney level profiles. This provides a possible explanation for the better tolerance of PCI-2022 relative to PCI-2050. Conclusion Hydrophilic sapphyrins were found to display promise as novel agents that localize to tumors, generate oxidative stress, and inhibit gene expression.
A retrospective case-control analysis of 2002 running injuries
Authors: J E Taunton, M B Ryan, D B Clement, D C McKenzie, D R Lloyd-Smith, B D Zumbo
Journal: British Journal of Sports Medicine (2002)

Objective: To provide an extensive and up to date database for specific running related injuries, across the sexes, as seen at a primary care sports medicine facility, and to assess the relative risk for individual injuries based on investigation of selected risk factors. Methods: Patient data were recorded by doctors at the Allan McGavin Sports Medicine Centre over a two year period. They included assessment of anthropometric, training, and biomechanical information. A model was constructed (with odds ratios and their 95% confidence intervals) of possible contributing factors using a dependent variable of runners with a specific injury and comparing them with a control group of runners who experienced a different injury. Variables included in the model were: height, weight, body mass index, age, activity history, weekly activity, history of injury, and calibre of runner. Results: Most of the study group were women (54%). Some injuries occurred with a significantly higher frequency in one sex. Being less than 34 years old was reported as a risk factor across the sexes for patellofemoral pain syndrome, and in men for iliotibial band friction syndrome, patellar tendinopathy, and tibial stress syndrome. Being active for less than 8.5 years was positively associated with injury in both sexes for tibial stress syndrome; and women with a body mass index less than 21 kg/m 2 were at a significantly higher risk for tibial stress fractures and spinal injuries. Patellofemoral pain syndrome was the most common injury, followed by iliotibial band friction syndrome, plantar fasciitis, meniscal injuries of the knee, and tibial stress syndrome. Conclusions: Although various risk factors were shown to be positively associated with a risk for, or protection from, specific injuries, future research should include a non-injured control group and a more precise measure of weekly running distance and running experience to validate these results.
Osteo-arthrosis and Disk Degeneration in an Urban Population
Authors: J. H. Kellgren, J. S. Lawrence
Journal: Annals of the Rheumatic Diseases (1958)

This study of osteo-arthrosis, or degenerative joint disease, is based on the same survey material as the corresponding paper on rheumatoid arthritis (Kellgren and Lawrence, 1956).A one-in-ten random sample of the population aged 55-64 years in the Lancashire town of Leigh was studied clini- cally, radiologically, and serologically for all forms of arthritis.After a detailed clinical examination of the joints, routine x rays were taken of the hands, feet, pelvis, knees, and cervical and lumbar spine, and a blood sample was taken for the sheep cell agglutination test (SCAT).The clinical and radio- logical part of the survey was 79 per cent.complete.In a previous survey of rheumatic complaints made in the town of Leigh in 1949-50, osteo-arthrosis was diagnosed on clinical grounds more frequently than any other form of rheumatism (Kellgren, Lawrence, and Aitken-Swan, 1953).The prevalence of com- plaints attributable to osteo-arthrosis was excep- tionally high in females over 50 years of age, and in this sex was more often polyarticular and was less closely associated with trauma or occupation than in males.A separate study of patients seen at the University Rheumatism Clinic had shown that women frequently suffer from a polyarticular form of osteo-arthrosis which has a distinct symptoma- tology, course, and pattern of joint involvement.This condition has been described as "primary generalized osteo-arthritis" (Kellgren and Moore, 1952).The present study was designed to obtain more precise information about this condition, and to investigate causative factors in osteo-arthrosis in general.For details of sampling and for the method of conducting the survey, the paper on rheumatoid arthritis should be consulted.At the clinical examination all persons seen were given a grading for rheumatoid arthritis and for local and generalized osteo-arthrosis.The x rays were later read by two observers in consultation.Problems of observer
Differential effects of nitric oxide on blood-brain barrier integrity and cerebral blood flow in intracerebral C6 gliomas
Authors: A. Weyerbrock, S. Walbridge, J. E. Saavedra, L. K. Keefer, E. H. Oldfield
Journal: Neuro-Oncology (2010)

Nitric oxide (NO) signaling in tumors and endothelial cells regulates vascular permeability and blood flow and therefore influences tumor uptake and response to therapeutic compounds.As delivery and efficacy of chemotherapy is impaired in CNS neoplasms due to a partially intact blood -brain barrier (BBB), we studied the effects of NO released by the short-acting NO donor disodium 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate methanolate (PROLI/NO) on BBB integrity and blood flow in C6 gliomas using [ 14 C]-aminoisobutyric acid (AIB) and [ 14 C]-iodoantipyrine quantitative autoradiography.PROLI/NO selectively increased intratumoral uptake of [ 14 C]AIB and [ 14 C]sucrose when given as a 3-minute intracarotid infusion or a 15-minute i.v.infusion (AIB: tumor, K 1 5 68.7 + + + + + 3.2 vs 24.9 + + + + + 0.9 mL g 21 min 21 , P < .0001;sucrose, K 1 5 16.9 + + + + + 0.9 vs 11.5 + + + + + 0.9 mL g 21 min 21 , P 5 .0007).This effect was achieved without significant changes in cerebral and tumor blood flow or arterial blood pressure, which indicates that the effect on vascular permeability is independent of changes in vascular tone induced by NO.This effect was mediated by activation of the NO/3',5'-cyclic guanosine monophosphate (cGMP) pathway, as it was blocked by guanylate cyclase inhibition by LY83583 and reproduced by the delivery of 8-bromoguanosine 5'-monophosphate or inhibition of cGMP degradation by the phosphodiesterase inhibitor zaprinast.Inhibition of inducible NO synthase by aminoguanidine or cyclooxygenase inhibition by indometacin or dexamethasone did not reduce the blood -tumor barrier (BTB) response to PROLI/NO.PROLI/NO, and perhaps other NOdonating compounds, can be used to selectively increase BTB permeability in gliomas through the NO/cGMP pathway at doses that do not cause unwanted vasodilatory changes in blood flow and that do not affect the systemic circulation.
CpG Oligodeoxynucleotides Alter Lymphocyte and Dendritic Cell Trafficking in Humans
Authors: W. Nicholas Haining, Jeffrey Davies, Holger Kanzler, Linda Drury, Thomas Brenn, John Evans, Jill Angelosanto, Steven Rivoli, Kate Russell, Suzanne George, Paul Sims, Donna Neuberg, Xiaochun Li, Jeffrey Kutok, Jeffrey Morgan, Patrick Wen, George Demetri, Robert L. Coffman, Lee M. Nadler
Journal: Clinical Cancer Research (2008)

Abstract Purpose: CpG oligodeoxynucleotides (CpG-ODN) are being investigated as cancer vaccine adjuvants because they mature plasmacytoid dendritic cells (PDC) into potent antigen-presenting cells. CpG-ODN also induce PDC to secrete chemokines that alter lymphocyte migration. Whether CpG-ODN TLR signals enhance antigen-specific immunity and/or trafficking in humans is unknown. Experimental Design: We conducted a phase I study of CpG-ODN (1018 ISS) given as a vaccine adjuvant with granulocyte-macrophage colony-stimulating factor (GM-CSF) to induce T-cell immunity to a peptide vaccine from the tumor-associated antigen hTERT. Results: The adjuvant effect was limited; only 1 of 16 patients showed a high-frequency hTERT-specific tetramer CD8+ T-cell response. However, CpG-ODN induced marked, transient peripheral blood lymphopenia. Biopsies showed dense lymphocytic infiltration at the vaccine site clustered around activated PDC. In vitro, CpG-ODN-treated PDC induced T-cell migration, showing that CpG-ODN stimulation of human PDC was sufficient to chemoattract T cells. Conclusions: Our results show that (a) CpG-ODN with GM-CSF may not be an effective adjuvant strategy for hTERT peptide vaccines but (b) GM-CSF/CpG-ODN causes a PDC-mediated chemokine response that recruits T-cell migration to the peripheral tissues. These findings suggest a novel therapeutic role for targeted injections of CpG-ODN to direct lymphocyte migration to specific sites such as the tumor bed.
SOME OBSERVATIONS ON AIRMEN WHO BREAK DOWN DURING BASIC TRAINING
Authors: ARI KIEV, MARTIN B. GIFFEN
Journal: American Journal of Psychiatry (1965)

Basic military training is one of the few planned experiences in our society that exposes late adolescents to a rapid series of physical as well as psychological stresses, and which consciously attempts to introduce changes in orientation and values. This paper examines some of the consistent patterns of stress present in basic military training in the USAF and some of the clinical features demonstrated by a group of 220 airmen hospitalized for acute psychiatric breakdown during such training. The factors making for poor adaptation are examined and the need for considering general coping mechanisms as opposed to conventional diagnostic categories is considered.
Update on Kaposi's sarcoma and other HHV8 associated diseases. Part 1: epidemiology, environmental predispositions, clinical manifestations, and therapy
Authors: Ulrich R Hengge, Thomas Ruzicka, Stephen K Tyring, Martin Stuschke, Michael Roggendorf, Robert A Schwartz, Siegfried Seeber
Journal: The Lancet Infectious Diseases (2002)
Airways Responses to Oral Ethanol in Normal Subjects and in Patients with Asthma
Authors: Jon Ayres, Patricia Ancic, T J H Clark
Journal: Journal of the Royal Society of Medicine (1982)

The effect of oral ethanol on airflow was studied in 5 normal subjects and 5 patients with asthma. On 4 different study days, each subject was asked to drink 40 ml of either water or 20%, 40% or 60% ethanol, and measurements were made of specific airways conductance (sGaw), blood ethanol levels, pulse rate and blood pressure. In some subjects in both groups there was a significant immediate fall in sGaw after drinking ethanol (below 5% confidence limits). Once absorbed, ethanol had a slight bronchodilator effect in 2 normal subjects and in 3 patients with asthma (5% level). Sixty per cent ethanol, when drunk slowly, showed significant bronchodilatation in 4 out of 5 patients with asthma and in one normal subject (5% level) with no acute fall in sGaw. Pulse rate and blood pressure did not change after water, 20% and 40% ethanol in either group, but immediately after 60% ethanol normal subjects showed a significant rise in pulse rate ( P &lt; 0.01) which was not seen in patients with asthma. The immediate changes in sGaw and pulse rate may be due to stimulation of irritant receptors in the upper airways. Ethanol may act directly on bronchial smooth muscle to produce bronchodilatation and may be useful as a bronchodilator when given intravenously.
Hypoglycemia and Risk of Cardiovascular Disease and All-Cause Mortality in Insulin-Treated People With Type 1 and Type 2 Diabetes: A Cohort Study
Authors: Kamlesh Khunti, Melanie Davies, Azeem Majeed, Brian Larsen Thorsted, Michael Lyng Wolden, Sanjoy K. Paul
Journal: Diabetes Care (2014)

OBJECTIVE Hypoglycemia has been associated with an increased risk of cardiovascular (CV) events and all-cause mortality. This study assessed whether, in a nationally representative population, there is an association between hypoglycemia, the risk of CV events, and all-cause mortality among insulin-treated people with type 1 diabetes or type 2 diabetes. RESEARCH DESIGN AND METHODS This retrospective cohort study used data from the Clinical Practice Research Datalink database and included all insulin-treated patients (≥30 years of age) with a diagnosis of diabetes. RESULTS In patients who experienced hypoglycemia, hazard ratios (HRs) for CV events in people with type 1 diabetes were 1.51 (95% CI 0.83, 2.75; P = ns) and 1.61 (1.17, 2.22), respectively, for those with and without a history of CV disease (CVD) before the index date. In people with type 2 diabetes, the HRs for patients with and without a history of CVD were 1.60 (1.21, 2.12) and 1.49 (1.23, 1.82), respectively. For all-cause mortality, HRs in people with type 1 diabetes were 1.98 (1.25, 3.17), and 2.03 (1.66, 2.47), respectively, for those with and without a history of CVD. Among people with type 2 diabetes, HRs were 1.74 (1.39, 2.18) and 2.48 (2.21, 2.79), respectively, for those with and without a history of CVD. The median time (interquartile range) from first hypoglycemia event to first CV event was 1.5 years (0.5, 3.5 years) and 1.5 years (0.5, 3.0 years), respectively, for people with type 1 and type 2 diabetes. CONCLUSIONS Hypoglycemia is associated with an increased risk of CV events and all-cause mortality in insulin-treated patients with diabetes. The relationship between hypoglycemia and CV outcomes and mortality exists over a long period.
Electrophysiological properties and responses to simulated ischemia in cat ventricular myocytes of endocardial and epicardial origin.
Authors: S Kimura, A L Bassett, T Furukawa, J Cuevas, R J Myerburg
Journal: Circulation Research (1990)

In multicellular preparations, there are differences in action potential configuration between endocardium and epicardium, and electrophysiological alterations induced by ischemia are more drastic in epicardium than in endocardium. The present study was designed to examine electrophysiological properties of single cardiac myocytes enzymatically isolated from the endocardial and epicardial surfaces of the cat left ventricle and to determine whether the differential responses to ischemia of intact tissue occur in single cells. Action potentials recorded from the isolated single cells of epicardial surface had lower action potential amplitude and a prominent notch between phase 1 and phase 2, compared with those of the cells isolated from the endocardial surface; these findings are similar to those in intact endocardial and epicardial preparations. Resting membrane potentials recorded from both endocardial and epicardial single cells were sensitive to the change in extracellular K+ concentration and had properties of a K+ electrode. Action potential duration was frequency dependent in both cell types and was shorter in epicardial cells than in endocardial cells at a stimulation rate of 3 Hz. When the cells were superfused with Tyrode's solution that was altered to mimic an ischemic environment in vivo (PO2, 30-40 mm Hg; pH 6.8; [K+], 10 mM; and glucose free), resting membrane potential, action potential amplitude, and action potential duration were reduced, and the refractory period was shortened in both endocardial and epicardial single cells, but there were no differences in the degree of changes in action potentials and refractory periods induced between the two cell types. Action potential changes induced by L-alpha-lysophosphatidylcholine (5-40 mg/l) were also similar in endocardial and epicardial single cells.(ABSTRACT TRUNCATED AT 250 WORDS)