tbuckley/cabot-search huggingface dataset:
Vector algebra in the analysis of genome-wide expression data
Authors: Finny G Kuruvilla, Peter J Park, Stuart L Schreiber
Journal: Genome biology (2002)

Data from thousands of transcription-profiling experiments in organisms ranging from yeast to humans are now publicly available. How best to analyze these data remains an important challenge. A variety of tools have been used for this purpose, including hierarchical clustering, self-organizing maps and principal components analysis. In particular, concepts from vector algebra have proven useful in the study of genome-wide expression data. Here we present a framework based on vector algebra for the analysis of transcription profiles that is geometrically intuitive and computationally efficient. Concepts in vector algebra such as angles, magnitudes, subspaces, singular value decomposition, bases and projections have natural and powerful interpretations in the analysis of microarray data. Angles in particular offer a rigorous method of defining 'similarity' and are useful in evaluating the claims of a microarray-based study. We present a sample analysis of cells treated with rapamycin, an immunosuppressant whose effects have been extensively studied with microarrays. In addition, the algebraic concept of a basis for a space affords the opportunity to simplify data analysis and uncover a limited number of expression vectors to span the transcriptional range of cell behavior. This framework represents a compact, powerful and scalable construction for analysis and computation. As the amount of microarray data in the public domain grows, these vector-based methods are relevant in determining statistical significance. These approaches are also well suited to extract biologically meaningful information in the analysis of signaling networks.
Augmented responses to vasoconstrictor stimuli in hypercholesterolemic and atherosclerotic monkeys.
Authors: D D Heistad, M L Armstrong, M L Marcus, D J Piegors, A L Mark
Journal: Circulation Research (1984)

We examined effects of hypercholesterolemia and atherosclerosis on vasoconstrictor responses to norepinephrine and serotonin. Responses were compared in normal, atherosclerotic, and hypercholesterolemic but non-atherosclerotic cynomolgus monkeys. The hindlimb was perfused at constant flow so that changes in perfusion pressure indicated changes in vascular resistance. We measured the pressure gradient from the iliac to the dorsal pedal artery so that responses of the large artery segment could be determined. Serotonin decreased total hindlimb resistance in normal and hypercholesterolemic monkeys, but increased total resistance in atherosclerotic monkeys. There was a greater than 10-fold increase in constrictor responses of large arteries to serotonin in atherosclerotic monkeys, compared with normal and hypercholesterolemic monkeys. In contrast, we found that vasoconstrictor responses to norepinephrine are normal in atherosclerotic monkeys and increased in hypercholesterolemic monkeys prior to development of atherosclerosis. Hypercholesterolemia augmented responses of small vessels to norepinephrine. We conclude that, during early stages of hypercholesterolemia in cynomolgus monkeys, vasoconstrictor responses to norepinephrine are increased in small vessels. At a later stage, as atherosclerosis develops, responses to norepinephrine return to normal, but vasoconstrictor effects of large arteries to serotonin are greatly potentiated.
Distribution of fibrinogen and albumin in normal, ischaemic, and necrotic myocardium during the evolution of myocardial infarction: an immunohistochemical study
Authors: M. C FISHBEIN, D. KULBER, M. STANCL, G. EDWALDS
Journal: Cardiovascular Research (1986)

The role of mediators of inflammation in the pathogenesis and evolution of myocardial infarction has attracted increased interest as interventions which inhibit the inflammatory response after coronary artery occlusion have been shown to decrease infarct size. The distribution of fibrinogen and albumin in ischaemia myocardium after closed chest balloon occlusion of the left anterior descending coronary artery was studied by immunohistochemical techniques in 34 dogs, and compared to morphological evaluation of cellular injury. In myocardium which was ischaemic but not necrotic (that is, glycogen loss and the absence of light and electron microscopic and tetrazolium staining evidence of necrosis, n = 8 dogs) no accumulation of these proteins was detected within the ischaemic zone. In myocardium which was necrotic by morphological criteria (n = 26 dogs), fibrinogen and albumin were detected in the necrotic fibres as early as 3 h after coronary occlusion using both the peroxidase-antiperoxidase and avidin-biotin immunostaining methods. Non-ischaemic myocardium never showed positive staining. The presence of fibrinogen and albumin in myocardial fibres appears to be specific for indicating irreversible injury.
Transmural Heterogeneity and Remodeling of Ventricular Excitation-Contraction Coupling in Human Heart Failure
Authors: Qing Lou, Vadim V. Fedorov, Alexey V. Glukhov, Nader Moazami, Vladimir G. Fast, Igor R. Efimov
Journal: Circulation (2011)

Background— Excitation-contraction (EC) coupling is altered in end-stage heart failure. However, spatial heterogeneity of this remodeling has not been established at the tissue level in failing human heart. The objective of this article was to study functional remodeling of excitation-contraction coupling and calcium handling in failing and nonfailing human hearts. Methods and Results— We simultaneously optically mapped action potentials and calcium transients in coronary perfused left ventricular wedge preparations from nonfailing (n=6) and failing (n=5) human hearts. Our major findings are the following. First, calcium transient duration minus action potential duration was longer at subendocardium in failing compared with nonfailing hearts during bradycardia (40 bpm). Second, the transmural gradient of calcium transient duration was significantly smaller in failing hearts compared with nonfailing hearts at fast pacing rates (100 bpm). Third, calcium transient in failing hearts had a flattened plateau at the midmyocardium and exhibited a 2-component slow rise at the subendocardium in 3 failing hearts. Fourth, calcium transient relaxation was slower at the subendocardium than at the subepicardium in both groups. Protein expression of sarcoplasmic reticulum Ca 2+ -ATPase 2a was lower at the subendocardium than the subepicardium in both nonfailing and failing hearts. Sarcoplasmic reticulum Ca 2+ -ATPase 2a protein expression at subendocardium was lower in hearts with ischemic cardiomyopathy compared with those with nonischemic cardiomyopathy. Conclusions— For the first time, we present direct experimental evidence of transmural heterogeneity of excitation-contraction coupling and calcium handling in human hearts. End-stage heart failure is associated with the heterogeneous remodeling of excitation-contraction coupling and calcium handling.
Chemopreventive Efficacy of Inositol Hexaphosphate against Prostate Tumor Growth and Progression in TRAMP Mice
Authors: Komal Raina, Subapriya Rajamanickam, Rana P. Singh, Rajesh Agarwal
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Herein, for the first time, we evaluated the in vivo chemopreventive efficacy of inositol hexaphosphate (IP6), a major constituent of high-fiber diets, against prostate tumor growth and progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Experimental Design: Beginning at 4 weeks of age, male TRAMP mice were fed 2% (w/v) IP6 in drinking water or only drinking water till 24 weeks of age, and then sacrificed. Prostate tissue was subjected to histopathologic analysis and to immunohistochemical analyses for proliferation and apoptosis. Results: IP6 feeding did not show any adverse effect on fluid and diet consumption and body weight. There was a significant reduction (40%; P &amp;lt; 0.01) in lower urogenital tract weight in IP6-fed mice. IP6 inhibited prostate cancer progression at prostatic intraepithelial neoplasia stage and strongly reduced the incidence of adenocarcinoma (prostatic intraepithelial neoplasia/adenocarcinoma, 75:25% in the IP6 group versus 39:61% in the control group; P &amp;lt; 0.05). The incidences of well-differentiated and poorly differentiated adenocarcinomas in the IP6-fed group were reduced by 44% and 62%, respectively. Immunohistochemical analysis of prostate tissue showed a 26% decrease (P &amp;lt; 0.05) in proliferation cell nuclear antigen–positive cells and a 3.5-fold increase in apoptotic cells with no effect on Tag expression by IP6. Conclusions: These findings are both novel and highly significant in establishing for the first time that oral IP6, without any toxicity, suppresses prostate tumor growth and progression at the neoplastic stage, thereby reducing the incidence of adenocarcinoma through its antiproliferative and proapoptotic effects, and thus indicating that IP6 could have potential chemopreventive effects against human prostate cancer.
On Nursing Systems
Authors: J. B. Hicks
Journal: BMJ (1880)

To some minds, the word " system" seems to have a magical import: what it really imports, it is scarcely thought necessary to follow out.In regard to the systems of nursing which are engaging our minds at present, it might be worth while to present to our views the leading features of those at present in vogue.For practical purposes, we may divide them into three kinds I.
Red Wine Intake Prevents Nuclear Factor-κB Activation in Peripheral Blood Mononuclear Cells of Healthy Volunteers During Postprandial Lipemia
Authors: Luis Miguel Blanco-Colio, Mónica Valderrama, Luis Antonio Alvarez-Sala, Carmen Bustos, Mónica Ortego, Miguel Angel Hernández-Presa, Pilar Cancelas, Juan Gómez-Gerique, Jesús Millán, Jesús Egido
Journal: Circulation (2000)

Background —Several epidemiological studies have demonstrated the beneficial effect of red wine intake in reducing total and cardiovascular mortality. This effect has been attributed in part to its antioxidant properties. Because the monocytes/macrophages and the nuclear transcription factor κB (NF-κB) are implicated in the pathogenesis of atherosclerotic lesions, we examined the effect of red wine intake on the activation of NF-κB in peripheral blood mononuclear cells. Methods and Results —Sixteen healthy volunteers were studied 3 times each: after a moderate dose, a low dose, and no wine with a fat-enriched breakfast. Lipid profile and NF-κB activation (electrophoretic mobility shift assay) were examined in blood samples taken before and 3, 6, and 9 hours after wine intake. In addition, mononuclear cells were incubated with VLDL in the presence of some antioxidants (quercetin and α-tocopherol succinate) contained in red wine to study their effects on NF-κB activation. Subjects receiving a fat-enriched breakfast had increased NF-κB activation in peripheral blood mononuclear cells coinciding with the augmentation in total triglycerides and chylomicrons. Red wine intake prevented NF-κB activity even though it induced a certain increase in serum lipids, particularly VLDL, that did not increase after the fat ingestion alone. However, another form of alcohol intake (vodka) did not modify the NF-κB activation provided by postprandial lipemia. In cultured mononuclear cells, isolated human VLDL caused NF-κB activation in a time-dependent manner that did not occur in the presence of the red wine antioxidants quercetin and α-tocopherol. Conclusions —Our results provide a new potential mechanism to explain the beneficial effects of red wine intake in the reduction of cardiovascular mortality.
First Outbreak of Hong Kong Influenza in a General Practice Population in Great Britain. A Field and Laboratory Study
Authors: R. E. Hope-Simpson
Journal: BMJ (1970)

The first outbreak of influenza caused by Hong Kong (H.K.) variant of type A(2) influenza virus in a general practice (3,620 persons) in Cirencester, England, lasted 13 weeks, from 15 January to 15 April 1969, and is estimated to have attacked 4% of the practice population. The epidemic was too small to produce much effect on the total respiratory morbidity, but when symptom groups were examined separately it could be clearly followed in the class "febrile respiratory disease" in which 76 of the 78 isolations of the virus were made.Liability to attack was almost independent of age except that persons over 65 were less frequently attacked. In household outbreaks neither schoolchildren nor children under school age were more commonly the first case than their elders. The occurrence of influenza within a household increased the risk of an attack four-fold for the other members, and subsequent cases all occurred within 10 days of the first-consecutive cases within six days of one another.It is planned to continue surveillance throughout the period of dominance of Hong Kong variants of type A(2) influenza virus.
Coronary and Myocardial Angiography
Authors: C. Michael Gibson, Albert Schömig
Journal: Circulation (2004)

2][3][4][5][6][7][8] It has become increasingly apparent, however, that clinical outcomes are not only associated with angiographic flow in the epicardial artery, but also with angiographic flow in the myocardium. 9 -13 To this end, the goal of reperfusion therapies has shifted to include reperfusion downstream at the level of capillary bed, and it might be more appropriate that the hypothesis now be termed "the time dependent open artery and open microvascular hypothesis."The goal of this article is to review angiographic methods used to evaluate myocardial ischemia and infarction and to discuss the insights into the pathophysiology of acute coronary syndromes provided by these angiographic indexes of coronary artery blood flow and myocardial perfusion.
Is Comorbidity of Posttraumatic Stress Disorder and Borderline Personality Disorder Related to Greater Pathology and Impairment?
Authors: Caron Zlotnick, C. Laurel Franklin, Mark Zimmerman
Journal: American Journal of Psychiatry (2002)

The authors examined whether patients with comorbid borderline personality disorder and posttraumatic stress disorder (PTSD) have a more severe clinical profile than patients with either disorder without the other.Outpatients with borderline personality disorder without PTSD (N=101), PTSD without borderline personality disorder (N=121), comorbid borderline personality disorder and PTSD (N=48), and major depression without PTSD or borderline personality disorder (N=469) were assessed with structured interviews for psychiatric disorders and for degree of impairment.Outpatients with diagnoses of comorbid borderline personality disorder and PTSD were not significantly different from outpatients with borderline personality disorder without PTSD, PTSD without borderline personality disorder, or major depression without PTSD or borderline personality disorder in severity of PTSD-related symptoms, borderline-related traits, or impairment.The additional diagnosis of PTSD or borderline personality disorder does little to augment the pathology or dysfunction of patients who have either disorder without the other.
Systemic and local immune responses against<i>Helicobacter pylori</i> urease in patients with chronic gastritis: distinct IgA and IgG productive sites
Authors: S Futagami, H Takahashi, Y Norose, M Kobayashi
Journal: Gut (1998)

Background — Helicobacter pylori urease is a major target for immune responses among various bacterial components in H pylori infected patients. Aims —To analyse the relation between systemic and local humoral immune responses to H pylori urease and grades of chronic gastritis. Patients —Seventy five patients with chronic gastritis associated with H pylori infection were classified into three groups (grade I, superficial gastritis; II, atrophic gastritis, quiescent; or III, atrophic gastritis, active). Methods —Anti- H pylori urease specific antibodies in the serum, gastric juice, and biopsy specimens were determined by ELISA or western blotting analysis. The sites for H pylori urease and its specific antibody producing B lymphocytes were confirmed by immunohistochemical analysis. Results —In the sera of patients with grade I gastritis, weak IgG but relatively strong IgA responses to H pylori urease were observed; dominant strong IgG responses were detected in grade II gastritis. In grade III gastritis, significant IgG and IgA responses were obtained. A similar pattern of IgA and IgG responses was detected in gastric juice and tissue. H pylori urease specific, antibody producing B cells were not found in the gastric mucosa of patients with grade I gastritis despite the presence of such B cells in the duodenal bulb. Specific B cells were observed in the gastric mucosa of patients with grade II and III gastritis with atrophy. Conclusions —Purified H pylori urease, together with localisation of its specific antibody producing B cells, are useful for serological testing and histopathological analysis for determining the stage of chronic gastritis and studying the pathogenesis of H pylori infection.
Safety of formoterol by Turbuhaler(R) as reliever medication compared with terbutaline in moderate asthma
Authors: P.W. Ind, C. Villasante, R.J. Shiner, A. Pietinalho, N.G. Böszörményi, S. Soliman, O. Selroos
Journal: European Respiratory Journal (2002)

The present study compared the safety of 4.5 µg formoterol with 0.5 mg terbutaline, both by Turbuhaler® and used as needed, in addition to regular formoterol in moderate asthma. In this double-blind parallel-group study, 357 patients taking a moderate-to-high dose of inhaled corticosteroids and additional terbutaline (2–5 inhalations·day −1 during run-in) were randomised to either formoterol or terbutaline as needed in addition to formoterol 9 µg b.i.d. over 12 weeks. Adverse events, serum potassium levels, electrocardiogram, vital signs and lung function were assessed monthly; peak expiratory flow and severe asthma exacerbations were recorded daily. Patients used 2.16 (range 0.0–6.3) formoterol and 2.34 (range 0.1–7.5) terbutaline relief inhalations·day −1 . No clinically significant differences in safety variables were found between treatments. Statistically greater increases in cardiac frequency (2.6 beats·min −1 , p=0.03) were found on terbutaline. There were 44 and 52 severe asthma exacerbations with formoterol and terbutaline, respectively, with no significant difference in time to first exacerbation. There was also no difference between treatments for other efficacy measures (peak expiratory flow, forced expiratory volume in one second and morning/evening symptom scores). Formoterol 4.5 µg as needed was at least as safe, well tolerated and effective as terbutaline 0.5 mg in stable patients (requiring up to 6 relief inhalations·day −1 ) taking formoterol plus inhaled corticosteroids regularly over 12 weeks.
THE COMPARTMENTALIZATION OF ANTIGEN-REACTIVE LYMPHOCYTES IN DESENSITIZED GUINEA PIGS
Authors: Stuart F. Schlossman, Howard A. Levin, Ross E. Rocklin, John R. David
Journal: The Journal of Experimental Medicine (1971)

A single injection of epsilon,DNP-Lys(7-10) can render previously sensitized guinea pigs specifically unreactive to subsequent intradermal challenge with that antigen. Antigen-reactive lymphocytes, as assayed by macrophage-migration in-inhibition or thymidine incorporation, were depleted from the peritoneal exudates of those animals. In contrast, it was intriguing to find that lymph node lymphocytes from such animals responded normally in the antigen-induced thymidine incorporation assay. These studies demonstrate a compartmentalization of antigen-reactive lymphocytes in desensitized animals which may account for the short-lived nature of this phenomenon.
Targeting people with pre-diabetes
Authors: K M V. Narayan
Journal: BMJ (2002)

Three major randomised controlled trials, conducted in diverse countries, settings, and populations, confirm that effective lifestyle intervention can prevent or delay the progression to type 2 diabetes in groups at high risk, such as overweight people with impaired glucose tolerance (glucose concentration 7.8-11.1 mmol/l, two hours after a 75 g loading).1–3 In the largest of these trials, the diabetes prevention programme in the United States, a lifestyle modification programme was delivered with the goals of at least a 7% weight loss and at least 150 minutes of physical activity per week.4 At 24 weeks, 50% of the participants in the lifestyle intervention group had achieved the weight loss goal and 74% had achieved the activity goal. In this trial, lifestyle intervention reduced the incidence of diabetes by 58%, and one case of diabetes was prevented for every 6.9 people treated for three years.3

In response to this impressive evidence, the American Diabetes Association's position statement on prevention of diabetes has recommended screening to detect people with impaired glucose tolerance or impaired fasting glucose (fasting …
Histological and biomechanical analysis of bone and interface reactions around hydroxyapatite-coated intramedullary implants of different stiffness: a pilot study on the goat
Authors: P. Buma, P.J.M. Van Loon, H. Versleyen, H. Weinans, T.J.J.H. Slooff, K. de Groot, R. Huiskes
Journal: Biomaterials (1997)
Renal Transplantation for Children
Authors: S. Michael Mauer
Journal: JAMA (1989)

To the Editor. —  In their commentary, Drs Reinhart and Kemph 1 express concern about the proportional benefit of renel transplantation in children. We agree that older children (6 to 7 years and older) should be included in the information and consent process and that their emerging autonomy must be respected. Unpleasant options including no active treatment, as well as the risks, costs, and inconveniences of all possible therapies, should be explored thoroughly. The lure of paternalism or unfair efforts to influence or limit the family's choices must be avoided. At the same time, the pediatrician must be the primary professional advocate for the patient and only secondarily for the family and society.  Unfortunately, the commentary by Drs Reinhart and Kemph is seriously inaccurate. While they pose an important question, it is placed in a 20-year-old time frame. Their references to the pediatric transplantation literature are out of date, most