tbuckley/cabot-search huggingface dataset:
Pathologic Changes in Aortic-Coronary Arterial Saphenous Vein Grafts
Authors: ZEEV VLODAVER, JESSE E. EDWARDS
Journal: Circulation (1971)

This is a pathologic study of segments of saphenous vein used as a graft between the aorta and a coronary artery in the surgical treatment of coronary atherosclerosis. Except for an occasional case with thrombotic occlusion of the graft, no lesions were observed in grafts which had been in place for less than 1 month. In each of two grafts in place for 1 month, mild fibrous thickening of the intima was present. Eight grafts which had been in place for 3½ months or longer consistently showed lesions, either organized thrombi (two grafts) or intimal fibrotic proliferative lesion (six grafts). In this group, five of the six grafts with intimal fibrous proliferation showed near or complete occlusion of the lumen. The intimal fibrous proliferative lesion appears primarily to be a response to arterial pressure within the segment of vein. Obstructive atherosclerosis in the artery beyond the anastomosis with the graft may favor the development of the intimal lesion. The intimal lesion may progress rapidly according to the data in one of the cases. In this, patency of the graft demonstrated angiographically 3½ months after the operation was followed by near-complete occlusion of the lumen by the proliferative lesion 3 weeks following demonstration of patency.
Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis
Authors: Verena Brune, Enrico Tiacci, Ines Pfeil, Claudia Döring, Susan Eckerle, Carel J.M. van Noesel, Wolfram Klapper, Brunangelo Falini, Anja von Heydebreck, Dirk Metzler, Andreas Bräuninger, Martin-Leo Hansmann, Ralf Küppers
Journal: The Journal of Experimental Medicine (2008)

The pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant nonneoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected L&H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&H cells to and/or that they originate from germinal center B cells at the transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell-rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive nuclear factor kappaB activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies.
Neutrophils in induced sputum arise from central airways
Authors: Y.P. Moodley, V. Krishnan, U.G. Lalloo
Journal: European Respiratory Journal (2000)

A high neutrophil count is often found in induced sputum compared to bronchoalveolar lavage fluid (BALF). This study investigated whether such a high neutrophil count may be a response to inhaled hypertonic saline or that the airway compartment sampled by induced sputum has a higher concentration of neutrophils than BALF. Saliva and induced sputum samples were taken at 10 and 20 min following inhalation of 3% hypertonic saline from an ultrasonic nebulizer in 12 healthy nonsmoking subjects. Four days later the 12 subjects underwent bronchoscopy (six following inhalation with 3% saline). Tracheal, proximal bronchial secretions, bronchial washings and BALF samples were obtained. The neutrophil count (% total leukocytes) increased significantly in saliva at 10 and 20 min post nebulization with 3% saline, although there was no change in neutrophils in induced sputum at 10 and 20 min. There was no significant difference in neutrophil count in the subjects who inhaled 3% saline as compared to those who did not, in secretions from the trachea, proximal bronchi, bronchial washings and BALF. Neutrophil counts were significantly higher in the trachea, proximal bronchi and bronchial washings as compared to BALF (p<0.001). It is concluded that neutrophil counts in healthy subjects increase from the peripheral towards the proximal airways, in the absence of hypertonic saline-induced changes. This suggests that the relatively high neutrophil count in induced sputum arises from the proximal airways and is not a response to inhaled hypertonic saline during the procedure.
A Phase I Trial of Enzastaurin in Patients with Recurrent Gliomas
Authors: Teri N. Kreisl, Lyndon Kim, Kraig Moore, Paul Duic, Svetlana Kotliarova, Jennifer Walling, Luna Musib, Donald Thornton, Paul S. Albert, Howard A. Fine
Journal: Clinical Cancer Research (2009)

Enzastaurin is a selective inhibitor of protein kinase C beta. Prior phase I studies did not show increased drug exposures with escalating once daily administration. Limits from gastrointestinal absorption may be overcome by twice daily dosing, potentially improving antitumor effects.We conducted a phase I dose escalation study in 26 patients with recurrent malignant glioma, stratified by use of enzyme-inducing antiepileptic drugs, to investigate whether divided twice daily dosing results in higher exposures compared with once daily dosing. Phosphorylated glycogen synthase 3 beta was analyzed as a potential biomarker of enzastaurin activity.Enzastaurin was poorly tolerated at all dose levels evaluated (500, 800, and 1,000 mg total daily), with thrombocytopenia and prolonged QTc as dose-limiting toxicities. The average drug concentration of enzastaurin under steady-state conditions was doubled by twice daily dosing compared with daily dosing [1.990; 90% confidence interval (CI), 1.450-2.730]. Additionally, geometric mean ratios doubled with 800 versus 500 mg dosing for both daily (2.687; 90% CI, 1.232-5.860) and twice daily regimens (1.852; 90% CI, 0.799-4.292). Two patients achieved long-term benefit (over 150 weeks progression free).Higher and more frequent dosing of enzastaurin resulted in improved drug exposure but with unacceptable toxicity at the doses tested. Phosphorylated glycogen synthase 3 beta may be a useful biomarker of the biological activity of enzastaurin. Enzastaurin has activity in a subset of malignant glioma patients and warrants continued study in combination with other agents using a maximal once daily dose of 500 mg.
Developing Global Maps of the Dominant Anopheles Vectors of Human Malaria
Authors: Simon I. Hay, Marianne E. Sinka, Robi M. Okara, Caroline W. Kabaria, Philip M. Mbithi, Carolynn C. Tago, David Benz, Peter W. Gething, Rosalind E. Howes, Anand P. Patil, William H. Temperley, Michael J. Bangs, Theeraphap Chareonviriyaphap, Iqbal R. F. Elyazar, Ralph E. Harbach, Janet Hemingway, Sylvie Manguin, Charles M. Mbogo, Yasmin Rubio-Palis, H. Charles J Godfray
Journal: PLoS Medicine (2010)

The Health in Action section is a forum for individuals or organizations to highlight their innovative approaches to a particular health problem.
Calcifying fibrous pseudotumour of the lung
Authors: M Peachell
Journal: Thorax (2003)

This paper updates the evidence base and key recommendations of the Health Education Authority (HEA) smoking cessation guidelines for health professionals published in <i>Thorax</i> in 1998. The strategy for updating the evidence base makes use of updated Cochrane reviews supplemented by individual studies where appropriate. This update contains additional detail concerning the effectiveness of interventions as well as comments on issues relating to implementation. The recommendations include clarification of some important issues addressed only in general terms in the original guidelines. The conclusion that smoking cessation interventions delivered through the National Health Service are an extremely cost effective way of preserving life and reducing ill health remains unchanged. The strategy recommended by the guidelines involves: (1) GPs opportunistically advising smokers to stop during routine consultations, giving advice on and/or prescribing effective medications to help them and referring them to specialist cessation services; (2) specialist smokers9 services providing behavioural support (in groups or individually) for smokers who want help with stopping and using effective medications wherever possible; (3) specialist cessation counsellors providing behavioural support for hospital patients and pregnant smokers who want help with stopping; (4) all health professionals involved in smoking cessation encouraging and assisting smokers in use of nicotine replacement therapies (NRT) or bupropion where appropriate. The key points of clarification of the previous guidelines include: (1) primary health care teams and hospitals should create and maintain readily accessible records on the current smoking status of patients; (2) GPs should aim to advise smokers to stop, and record having done so, at least once a year; (3) inpatient, outpatient, and pregnant smokers should be advised to stop as early as possible and the advice recorded in the notes in a readily accessible form; (4) there is currently little scientific basis for matching individual smokers to particular forms of NRT; (5) NHS specialist smokers9 clinics should be the first point of referral for smokers wanting help beyond what can be provided through brief advice from the GP; (6) help from trained health care professionals specialising in smoking cessation such as practice nurses should be available for smokers who do not have access to specialist clinics; (7) the provision of specialist NHS smokers9 clinics should be commensurate with demand; this is currently one or two full time clinics or their equivalent per average sized health authority, but demand may rise as publicity surrounding the services increases.
Inferring transcriptional modules from ChIP-chip, motif and microarray data.
Authors: Karen Lemmens, Thomas Dhollander, Tijl De Bie, Pieter Monsieurs, Kristof Engelen, Bart Smets, Joris Winderickx, Bart De Moor, Kathleen Marchal
Journal: Genome biology (2006)

Abstract 'ReMoDiscovery' is an intuitive algorithm to correlate regulatory programs with regulators and corresponding motifs to a set of co-expressed genes. It exploits in a concurrent way three independent data sources: ChIP-chip data, motif information and gene expression profiles. When compared to published module discovery algorithms, ReMoDiscovery is fast and easily tunable. We evaluated our method on yeast data, where it was shown to generate biologically meaningful findings and allowed the prediction of potential novel roles of transcriptional regulators.
A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION
Authors: Michael Heidelberger, Henry P. Treffers, Manfred Mayer
Journal: The Journal of Experimental Medicine (1940)

1. In two rabbits subjected to prolonged injections with crystalline egg albumin the antibodies in one showed progressive changes such as noted in an earlier paper; the antibodies in the other did not. 2. The significance of this behavior in the production of sera for therapeutic use is pointed out. 3. Quantitative studies are reported on the low grade or incomplete antibody present in the early stages of immunization of a horse with egg albumin. 4. Quantitative studies on the flocculating antibody from later bleedings from the horse are given, and the dissociation of the soluble pre-zone compounds by rabbit anti-egg albumin is studied. Rough velocity estimations are reported. 5. The bearing of the findings on the mechanism of precipitin and flocculation reactions and of the Danysz effect is discussed in terms of the union of multivalent antigen with multivalent antibody.
Renal tubular cell protein breakdown in uninephrectomized and ammonium chloride-loaded rats.
Authors: P Shechter, J D Shi, R Rabkin
Journal: Journal of the American Society of Nephrology (1994)

Kidney enlargement after unilateral nephrectomy or the induction of a systemic acidosis with ammonium chloride is associated with an increase in kidney protein content. This reflects an imbalance between protein breakdown and protein synthesis. Because it has been shown in diabetic nephromegaly that depressed protein breakdown contributes to the increase in kidney protein content, this study examined whether altered protein breakdown is common to all forms of renal hypertrophy. Accordingly, protein turnover was measured in isolated proximal tubules from kidney in rats undergoing renal enlargement after uninephrectomy or chronic ammonium chloride-induced acidosis. In both conditions, kidney protein content and protein synthesis ([14C]valine incorporation) increased significantly. Fractional protein degradation was depressed in renal tubules isolated from the acidotic rats and was accompanied by a decrease in proximal tubule cathepsin B and combined B and L activities. These changes are comparable to earlier observations with the diabetic kidney. In contrast, after unilateral nephrectomy, protein breakdown is not reduced, and it can reasonably be concluded that, in this condition, protein gain reflects increased protein synthesis alone. It was concluded that the pattern of protein turnover leading to protein accretion in renal hypertrophy varies according to the initial stimulus for renal growth.
Effect of Cigarette Smoking and Breathing Carbon Monoxide on Cardiovascular Hemodynamics in Anginal Patients
Authors: WILBERT S. ARONOW, JOHN CASSIDY, JACK S. VANGROW, HAROLD MARCH, JOHN C. KERN, JOHN R. GOLDSMITH, MAHAVEER KHEMKA, JAMES PAGANO, MICHAEL VAWTER
Journal: Circulation (1974)

Smoking high-nicotine cigarettes caused a significant increase in systolic and diastolic arterial pressure, heart rate, left ventricular end-diastolic pressure, and coronary sinus, arterial, and venous CO levels, no significant change in left ventricular dp/dt, aortic systolic ejection period, and cardiac index, and a significant decrease in stroke index and coronary sinus, arterial, and venous PO 2 levels in eight anginal patients with documented coronary disease. One week later, these patients inhaled 150 ppm of carbon monoxide until their increase in coronary sinus CO was similar to that produced after smoking their third cigarette. Inhaling carbon monoxide caused a significant increase in left ventricular end-diastolic pressure and coronary sinus, arterial, and venous CO levels, no significant change in systolic and diastolic arterial pressure, heart rate, and systolic ejection period, and a significant decrease in left ventricular dp/dt, stroke index, cardiac index, and coronary sinus, arterial, and venous PO 2 levels. Nicotine caused the increased systolic and diastolic arterial pressure and heart rate after smoking. Carbon monoxide caused the negative inotropic effect which increased the left ventricular end-diastolic pressure and decreased the stroke index after smoking.
Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps
Authors: Sarah Peterson, Julie A. Poposki, Deepti R. Nagarkar, Regina T. Chustz, Anju T. Peters, Lydia A. Suh, Roderick Carter, James Norton, Kathleen E. Harris, Leslie C. Grammer, Bruce K. Tan, Rakesh K. Chandra, David B. Conley, Robert C. Kern, Robert P. Schleimer, Atsushi Kato
Journal: Journal of Allergy and Clinical Immunology (2011)
Response to Comment on: Hermida et al. Influence of Time of Day of Blood Pressure–Lowering Treatment on Cardiovascular Risk in Hypertensive Patients With Type 2 Diabetes. Diabetes Care 2011;34:1270–1276
Authors: Ramón C. Hermida, Diana E. Ayala, Artemio Mojón, José R. Fernández
Journal: Diabetes Care (2011)

We thank Rossen and Hansen (1) for their interest in our article (2). The participants represented a consecutive series of patients fulfilling the exclusion/inclusion criteria who were recruited from those referred to the hospital for evaluation by ambulatory blood pressure monitoring (ABPM) mainly to confirm or reject the diagnosis of hypertension inferred by clinic cuff blood pressure measurement. Diagnosis of hypertension in our trial was based on accepted ABPM criteria, i.e., an awake systolic blood pressure (SBP)/diastolic blood pressure (DBP) mean ≥135/85 mmHg and/or an asleep SBP/DBP mean ≥120/70 mmHg (3). Despite a recommended target goal for clinic SBP/DBP in diabetes of 130/80 mmHg, current guidelines do not provide separate ABPM threshold values for patients with and without diabetes (3). Patients with diabetes in our trial …
Transfection of human endothelial cells
Authors: Felix C Tanner, Dianne P Carr, Gary J Nabel, Elizabeth G Nabel
Journal: Cardiovascular Research (1997)

Objective: The introduction of recombinant genes into endothelial cells provides a method to study specific gene products and their effect on cell function. In addition, endothelial cells can be used for implantation into vessels or prosthetic vascular grafts. Because transfection efficiencies in human endothelial cells have been low, it is important to develop improved gene transfer techniques. Therefore, several transfection methods were optimized and transfection efficiencies were determined. Methods: Transfection by particle-mediated gene transfer (biolistics) or by cationic liposomes were optimized and compared to calcium phosphate and DEAE-dextran. Transfection efficiency was determined using either a β-galactosidase or placental alkaline phosphatase reporter gene. The effect of promoter strength was analyzed by transfecting plasmids with either the Rous sarcoma virus (RSV) promoter or cytomegalovirus (CMV) promoter regions. Results: Optimal conditions for particle-mediated gene transfer utilized gold particles of 1.6 μm diameter, a target distance of 3 cm, helium pressures of 8.96 MPa (1300 psi) and cell confluence of 75%. Transfection with different cationic liposomes demonstrated that one compound, N-(3-aminopropyl)-N,N-dimethyl-2,3-(bis-dodecyloxy)-1-propaniminium bromide/dioleoyl phosphatidylethanolamine (γAP-DLRIE/DOPE), was optimal for gene transfer when 5 μg of DNA and 10 to 20 μg of lipid was used. With both gold particles and γAP-DLRIE/DOPE, the alkaline phosphatase reporter was more efficient than β-galactosidase using comparable promoters and polyadenylation sites. CMV regulatory elements were more efficient than the RSV promoter in optimizing gene expression. Optimal gene transfer efficiency was 20.28% of cells with γAP-DLRIE/DOPE, 3.96% with biolistics, 2.09% with calcium phosphate and 0.88% with DEAE-dextran. Conclusions: Gene expression is detectable in a high percentage of human endothelial cells after liposome-mediated transfection when expression is controlled by a strong promoter. Particle-mediated transfection is less efficient under these conditions, but more effective than liposomes when expression is driven by a relatively weak promoter. Calcium phosphate and DEAE-dextran are less useful.
A phonological perspective on locus equations
Authors: William J. Idsardi
Journal: Behavioral and Brain Sciences (1998)

Locus equations fail to provide adequate abstraction to capture the English phoneme /g/. They also cannot characterize final consonants or their relation to pre-vocalic consonants. However, locus equations are approximately abstract enough to define the upper limit on phonological distinctions for place of articulation. Hence, locus equations seem to mediate phonetic and phonological perceptual abilities.
New public health system is marred by confusion and lack of accountability, say MPs
Authors: A. O'Dowd
Journal: BMJ (2013)

The new public health system starting next month in England is flawed in several ways, including confused accountability and questions over who would be in charge during health emergencies, MPs have warned.

Overall, MPs on the parliamentary Communities and Local Government Committee have welcomed the return of responsibility for improving the general health and wellbeing of local people from the NHS to local government, but they say that many issues still have to be resolved.

In its new report the committee said that it had concerns over the complex accountability mechanisms of the new system.1

One example was the lack of clarity over who would be in …
Relationship Between Lineprotein Profile and Urinary Albumin Excretion in Type II Diabetic Patients With Stable Metabolic Control
Authors: Jordi L Reverter, Eduarda Pizarro, Marian Sentí, Juan Pedro-Botet, Juan Rubiés-Prat, Ramón Romero, Anna Lucas, Anna Sanmartí, Isabel Saunas
Journal: Diabetes Care (1994)

OBJECTIVE To assess lipids and lipoprotein composition and the relationship between lipoprotein abnormalities and urinary albumin excretion (UAE) in select type II diabetic patients with stable metabolic control. RESEARCH DESIGN AND METHODS Fifty-five type II diabetic patients and 55 healthy control subjects both with a body mass index &amp;lt;30 kg/m2 were studied. Patients were classified according to their level of UAE as normoalbuminuric (n = 37), microalbuminuric (n = 11), and macroalbuminuric (n = 7). In all cases, serum creatinine and albumin concentrations were in the normal range. RESULTS Normoalbuminuric patients showed increased triglyceride (TG) contents in intermediate-density lipoprotein (IDL) (P &amp;lt; 0.01), low-density lipoprotein (LDL) (P &amp;lt; 0.001), and high-density lipoprotein (HDL) (P &amp;lt; 0.001) compared with control subjects. Lipoprotein concentration in microalbuminuric patients did not differ from that of normoalbuminuric patients. On the other hand, patients with macroalbuminuria showed a significant increase in IDL cholesterol (P &amp;lt; 0.01) and IDL (P &amp;lt; 0.01), LDL (P &amp;lt; 0.05), and HDL TGs (P &amp;lt; 0.01) compared with the other groups. Diabetic patients with nephropathy, both microalbuminuric and macroalbuminuric, tended to have higher mean lipoprotein(a) (Lp[a]) concentrations than normoalbuminuric patients and control subjects. A strongly positive correlation was observed between UAE and serum TGs (r = 0.56) and very-low-density lipoprotein (r = 0.55), IDL (r = 0.52), LDL (r = 0.54), and HDL TGs (r = 0.52). CONCLUSIONS Lipoprotein alterations observed in diabetic patients, specifically IDL abnormalities and a tendency toward high Lp(a) levels, which are more marked in those with increased UAE, may contribute to the excess of cardiovascular disease in type II diabetic patients, particularly those with nephropathy.
Role of extracellular zinc and copper on metallothionein regulation in cultured rat hepatocytes*1
Authors: J HIDALGO
Journal: Hepatology (1991)

Cellular and extracellular metallothionein contents of rat hepatocytes cultured in the presence of albumin (30 mumol/L) with zinc (1, 10, 50 and 100 mumol/L), copper (1, 10 and 50 mumol/L), zinc and copper (1, 10 and 50 mumol/L of each metal) or no metals in the culture medium have been measured by radioimmunoassay. Cellular metallothionein levels increased steadily with culture time regardless of the metal treatment and showed little dependence (only a twofold increase) on extracellular zinc or copper at all metal concentrations and times (up to 3 days) studied. In contrast, the presence of both metals simultaneously in the culture medium strongly increased cellular metallothionein contents, acting synergistically in some cases. Significant extracellular metallothionein was observed when copper or zinc and copper were present in the culture medium, most of which is likely a consequence of cell leakage because no evidence of physiological secretion was observed. Total metallothionein production (cellular and extracellular metallothionein levels) indicated that copper was a better metallothionein inducer than zinc in these experimental conditions. These results indicate that metallothionein regulation in the hepatocyte is different depending on the extracellular metal levels and composition and that attention must be given to metallothionein release from the hepatocyte.