tbuckley/cabot-search huggingface dataset:
Wnt Signaling Mediates Pathological Vascular Growth in Proliferative Retinopathy
Authors: Jing Chen, Andreas Stahl, Nathan M. Krah, Molly R. Seaward, Roberta J. Dennison, Przemyslaw Sapieha, Jing Hua, Colman J. Hatton, Aimee M. Juan, Christopher M. Aderman, Keirnan L. Willett, Karen I. Guerin, Akiko Mammoto, Matthew Campbell, Lois E.H. Smith
Journal: Circulation (2011)

Ischemic proliferative retinopathy, characterized by pathological retinal neovascularization, is a major cause of blindness in working-age adults and children. Defining the molecular pathways distinguishing pathological neovascularization from normal vessels is critical to controlling these blinding diseases with targeted therapy. Because mutations in Wnt signaling cause defective retinal vasculature in humans with some characteristics of the pathological vessels in retinopathy, we investigated the potential role of Wnt signaling in pathological retinal vascular growth in proliferative retinopathy.In this study, we show that Wnt receptors (Frizzled4 and low-density lipoprotein receptor-related protein5 [Lrp5]) and activity are significantly increased in pathological neovascularization in a mouse model of oxygen-induced proliferative retinopathy. Loss of Wnt coreceptor Lrp5 and downstream signaling molecule dishevelled2 significantly decreases the formation of pathological retinal neovascularization in retinopathy. Loss of Lrp5 also affects retinal angiogenesis during development and formation of the blood-retinal barrier, which is linked to significant downregulation of tight junction protein claudin5 in Lrp5(-/-) vessels. Blocking claudin5 significantly suppresses Wnt pathway-driven endothelial cell sprouting in vitro and developmental and pathological vascular growth in retinopathy in vivo.These results demonstrate an important role of Wnt signaling in pathological vascular development in retinopathy and show a novel function of Cln5 in promoting angiogenesis.
Brightest X-rays Ever Give Researchers Brand-new View of Biological Molecules
Authors: Andrew A. Skolnick
Journal: JAMA (1994)

BY THE SUMMER of 1995, scientists at the Argonne National Laboratory near Chicago, Ill, expect to switch on the brightest beams of light ever to shine on the earth. The light, in the form of synchrotron x-rays, will be used to study the nature of materials, including toxins, enzymes, cell receptors, viral proteins, and other biological molecules. When fully operational, the Advanced Photon Source at Argonne is expected to provide superintense beams of x-rays for up to 70 separate experiments at a time in medicine, biotechnology, chemistry, physics, materials science, geoscience, and other fields of basic and applied research. The x-ray beams will be 10 000 times brighter than any source now available for research. <h3>World's Largest Microscope Light</h3> The enormously bright and very short wavelength light should enable researchers to capture detailed images of the atomic structure and behavior of complex biological molecules. Because of the great intensity of
An assessment of radical prostatectomy. Time trends, geographic variation, and outcomes. The Prostate Patient Outcomes Research Team
Authors: G. L. Lu-Yao
Journal: JAMA (1993)

To examine temporal trends and geographic variation in radical prostatectomy rates and short-term outcomes.Population-based study of radical prostatectomy for the years 1984 through 1990. Poisson regression was used to estimate temporal and regional effects.The 50 states and the District of Columbia.A 20% national sample of male Medicare beneficiaries aged 65 years or older.Rate of radical prostatectomy; 30-day mortality; and major cardiopulmonary complications, vascular complications, or surgical repairs within 30 days of radical prostatectomy.A total of 10,598 radical prostatectomies were identified. The adjusted rate of radical prostatectomy in 1990 was 5.75 times that in 1984. The relative increase was similar in all age groups. Substantial geographic variation existed in rates from 1988 through 1990: all states in the New England and Mid-Atlantic regions had rates equal to or below 60 per 100,000 male Medicare beneficiaries, while all states in the Pacific and Mountain regions had rates equal to or above 130 per 100,000. The mortality and morbidity after radical prostatectomy are not trivial for older men (aged 75 years and older)--almost 2% died and nearly 8% suffered major cardiopulmonary complications within 30 days of the operation.The sharp increase and wide geographic variation in radical prostatectomy rates make the evaluation of this surgical procedure a pressing issue. The rising rate of radical prostatectomy among men aged 75 years and older merits special attention.
Immunological features in multiple sclerosis.
Authors: G Lamoureux, N Giard, R Jolicoeur, V Toughlian, M Desrosiers
Journal: BMJ (1976)

A clinical and laboratory profile of the immunological system of patients with multiple sclerosis (MS) strongly suggested that many specific immune deficiencies exist in MS. The immunological history showed that patients with MS had had more tonsillectomies, appendicectomies, and childhood infections than matched controls, which suggested that there had been problems in controlling various types of childhood infections. The cell-mediated immune response and the circulating antibody titres were specifically impaired against a variety of antigens. Patients with MS had significantly lower serum antibody titres than controls against many naturally occurring antigens-namely, diptheria and tetanus toxoids, adenovirus, and mumps viruses. Raised serum antibody titres were found against measles and varicella zoster viruses while no difference was found towards other antigens. The delayed hypersensitivity reaction and the immunological memory of patients with MS were also greatly reduced against the mumps skin test antigens. There were normal amounts of circulating T and B lymphocytes, and the phytohaemagglutinin, concanavallin A, pokeweed mitogen, and encephalitogens lymphocyte transformation was not different from that in controls. These results indicated that patients with MS have more infectious problems than normal people and that both their T and B cell systems cannot mount a fully normal immunological response to some viral and bacterial antigens, while they give an increased response to others.
Diphenhydramine Abuse and Withdrawal
Authors: Lewis Glickman
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The letter of Feldman and Behar<sup>1</sup>describes the withdrawal of a patient dependent on 1600 mg of diphenhydramine hydrochloride per day. As far as I am aware it is the first report of abuse of diphenhydramine as found in Sominex 2, an over-the-counter sleep aid, and thus alerts the physician to the potential for abuse of this drug. I disagree, however, with the authors' statement that "increased defecation was the only cholinergic rebound effect noted even with rapid tapering." They also point out that "this patient did display moderate irritability and restlessness as the drug use was stopped" and insomnia characterized by "getting up and lying down repeatedly." The authors described this as a bedtime ritual of such magnitude that it led to the patient signing out on day 15 "following a disagreement with the staff over his bedtime behavior." This behavior resembles the akathisialike syndrome reported
Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance.
Authors: J J Kenny, C M Moratz, G Guelde, C D O'Connell, J George, C Dell, S J Penner, J S Weber, J Berry, J L Claflin
Journal: The Journal of Experimental Medicine (1992)

Antibodies bearing the T15 idiotype dominate the murine primary immune response to phosphocholine (PC). Analysis of antigen binding of antibodies derived from V1:DFL16.1:JH1 (VH1) germline and N region-derived variant heavy (H) chains and kappa 22, kappa 24, and kappa 8 light (L) chains demonstrates that the T15H:kappa 22L (T15) antibody binds PC at least 20-40 times better than other antibodies derived from alternate germline forms of the VH1 H chain and kappa 22, kappa 24, or kappa 8 L chains. To achieve affinities in the same range as the T15 antibody, kappa 24 and kappa 8 L chain-containing antibodies must have H chains derived from variant N region or somatically mutated VH1 genes. Single amino acid differences at the VD junction of the various germline and N region variant VH1 H chains dictate the L chain that can associate with the H chain to produce a PC-specific antibody. Several H:L combinations give rise to T15 or M167 idiotype-positive antibodies that lack specificity for PC, and single amino acid substitutions or insertions at the VH1:D junction result in the loss of T15 or M167 idiotopes. Based on these observations, our data support a molecular model involving both preferential gene rearrangement and antigen-driven B cell selection to explain T15 idiotype dominance in the immune response to PC. In the absence of N region diversification, large numbers of neonatal B cells bearing the T15H:kappa 22L surface immunoglobulin M (sIgM) receptors would be selected and expanded by autologous or environmental PC antigen into the long-lived peripheral B cell pool.
Multifunctional receptor-targeted nanocomplexes for the delivery of therapeutic nucleic acids to the Brain
Authors: Gavin D. Kenny, Alison S. Bienemann, Aristides D. Tagalakis, John A. Pugh, Katharina Welser, Frederick Campbell, Alethea B. Tabor, Helen C. Hailes, Steven S. Gill, Mark F. Lythgoe, Cameron W. McLeod, Edward A. White, Stephen L. Hart
Journal: Biomaterials (2013)

Convection enhanced delivery (CED) is a method of direct injection to the brain that can achieve widespread dispersal of therapeutics, including gene therapies, from a single dose. Non-viral, nanocomplexes are of interest as vectors for gene therapy in the brain, but it is essential that administration should achieve maximal dispersal to minimise the number of injections required. We hypothesised that anionic nanocomplexes administered by CED should disperse more widely in rat brains than cationics of similar size, which bind electrostatically to cell-surface anionic moieties such as proteoglycans, limiting their spread. Anionic, receptor-targeted nanocomplexes (RTN) containing a neurotensin-targeting peptide were prepared with plasmid DNA and compared with cationic RTNs for dispersal and transfection efficiency. Both RTNs were labelled with gadolinium for localisation in the brain by MRI and in brain sections by LA-ICP-MS, as well as with rhodamine fluorophore for detection by fluorescence microscopy. MRI distribution studies confirmed that the anionic RTNs dispersed more widely than cationic RTNs, particularly in the corpus callosum. Gene expression levels from anionic formulations were similar to those of cationic RTNs. Thus, anionic RTN formulations can achieve both widespread dispersal and effective gene expression in brains after administration of a single dose by CED.
Drug Substitution Encouraged by Law
Authors: Sheldon S. Stoffer
Journal: JAMA (1981)

To the Editor.—  We have previously cautioned that generic levothyroxine sodium tablets are not always equivalent to a brand name product. We stressed that until such time that levothyroxine products become more uniform, physicians, pharmacists, and legislators should not encourage product switching (1980;244:1704). We suspect that other generic drugs may also not always be equivalent to brand name products. Current regulatory agencies seem unable to monitor adequately and ensure uniformity of the vast number of generic drugs.   1981 state of Michigan fiscal appropriation bill for social services provides a Medicaid pharmaceutical dispensing fee of $2.65 when a generic drug is dispensed and $2.15 when a brand name drug is dispensed. A 50-cent copayment per prescription is required from Medicaid patients older than 21 years when some brand name drugs are dispensed where generic equivalents are available. The copayment may be requested by the pharmacy before filling the prescription and,
The Symptom Complex of Familial Sinus Node Dysfunction and Myocardial Noncompaction Is Associated With Mutations in the HCN4 Channel
Authors: Patrick A. Schweizer, Julian Schröter, Sebastian Greiner, Jan Haas, Pessah Yampolsky, Derliz Mereles, Sebastian J. Buss, Claudia Seyler, Claus Bruehl, Andreas Draguhn, Michael Koenen, Benjamin Meder, Hugo A. Katus, Dierk Thomas
Journal: Journal of the American College of Cardiology (2014)
Monitoring of alveolar macrophage production of tumor necrosis factor-alpha and interleukin-6 in lung transplant recipients. Marseille and Montreal Lung Transplantation Group.
Authors: A Magnan, J L Mege, M Reynaud, P Thomas, C Capo, L Garbe, B Meric, M Badier, P Bongrand, L Viard
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Bronchiolitis obliterans (BO), a common complication in lung transplant recipients, is a fibrotic process probably related to acute rejection (AR) and cytomegalovirus pneumonitis (CMVP). Because the pathogenesis of pulmonary fibrotic diseases involves activation of alveolar macrophages (AM), the present study was carried out to determine if AM were activated during AR, CMVP, and BO. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured in 157 AM supernatants obtained from 29 transplant recipients by immunoradiometric assay. Five groups were analyzed: AR (n = 21), CMVP (n = 12), BO (n = 15), bacterial pneumonia (BP) (n = 8), and control subjects (n = 70). Cytokines were also assayed 15 d (n = 15) and 30 d (n = 9) after AR and 30 d (n = 9) after CMVP. Cytokine secretion was elevated during AR (TNF-alpha = 3,709 +/- 1,409 pg/10(6) cells, IL-6 = 5,482 +/- 2,058 pg/10(6) cells, p < 0.005), and they returned to control values within 15 d. A similar pattern was observed during CMVP (TNF-alpha = 5,000 +/- 2,773 pg/10(6) cells, IL-6 = 12,280 +/- 3,939 pg/10(6) cells, p < 0.005), and values returned to control levels within 30 d. During BP, cytokine production values were higher than control values, but to a lesser extent than in AR and CMVP (TNF-alpha = 2,502 +/- 1,072, p < 0.05; IL-6 = 3,734 +/- 1,440, p < 0.005). In contrast, cytokine secretion during BO was not statistically different from that of control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Endoscopic Management of Upper Gastrointestinal Polyps and Periampullary Lesions in Familial Adenomatous Polyposis and Gardner's Syndrome
Authors: R. van Stolk, M. V. Sivak, Jr., J. L. Petrini, R. Petras, D. R. Ferguson, D. Jagelman
Journal: Endoscopy (1987)

Upper gastrointestinal polyps and carcinoma, especially of the periampullary area, may occur in patients with familial adenomatous polyposis. Upper gastrointestinal polyps were present in about 43% of patients in the polyposis registry of the Cleveland Clinic who underwent screening esophagogastroduodenoscopy. Approximately one-third of these polyps were neoplastic. Three distribution patterns were recognized: 1. fundic, 2. duodenal, and 3. fundic plus duodenal. Despite the occurrence of a few gastric cancers in patients with familial adenomatous polyposis, the risk of carcinoma of the major duodenal papilla and periampullary area is more significant. It is necessary to examine the duodenal papilla with a side-viewing instrument and to obtain biopsy specimens from this structure in these patients. The major duodenal papilla was abnormal in about one-half of our patients in whom this structure was specifically examined with a side-viewing endoscope. The preliminary results of a trial of endoscopic treatment of upper gastrointestinal polyps and lesions of the major duodenal papilla in patients with familial adenomatous polyposis are described.
Hyperbaric Oxygen Toxicity Prevention With Succinate
Authors: Aaron P. Sanders
Journal: JAMA (1968)

Succinate protection against oxygen toxicity in rats was investigated at oxygen pressures of 5, 7, 9, and 11 atmospheres absolute (atm abs), and compared with protection given by dextrose and malate. Times to convulsions were used for comparison. Dextrose and malate gave no protection. Succinate provided relatively long-term protection at 5 and 7 atm abs oxygen exposures, but showed decreasing protection with increasing pressure. Succinate provided no protection at oxygen pressures of 12 atm abs or higher. A 3:1 sodium succinate:ammonium succinate mixture (0.4M, pH 7.4) solved the problem of alkalosis previously encountered with a sodium succinate solution. The infusion of the 3:1 mixture (6 millimols/kg/hr) in dogs exposed to 5 atm abs oxygen delayed convulsion 5 to 11 times longer than in controls. Intracellular localization and thin layer chromatography studies with succinate-2, 3<sup>14</sup>C showed that succinate readily penetrated the blood brain barrier.
OT2-03-03: Spectroscopic Feature of Breast Cancer.
Authors: H Ogura, D Yamashita, H Nasu, Y Hosokawa, K Koizumi, E Yamaki, K Yoshimoto, T Suzuki, Y Ueda, M Oda, Y Yamashita, H Sakahara
Journal: Cancer Research (2011)

Abstract Objectives: To examine optical properties of breast cancer by time-resolved spectroscopy. Materials and Methods: We irradiated a pulsed laser of 760, 800, and 830 nm wave-length lights at multiple sites of both breasts including the site just above the cancer and detected the light transmitted through the breast with TRS-20SH (Hamamatsu Photonics K.K.). Absorption coefficient (μa), reduced scattering coefficient (μs'), total hemoglobin (tHb), and oxygen saturation (SO2) of the breast were calculated by photon diffusion equation. The clinical trial started in January 2007. A total of one hundred nine breast cancer patients participated in the trial and written informed consent were obtained from all of the patients. Results: In 800 nm wave-length, absorption coefficient (μa) of breast cancer tissue was significantly high, compared with contra-lateral normal breast (cancer:0.0677± 0.0293, normal breast;0.0479± 0.0161, p&amp;lt;0.001). The result was the same in 760, and 830 nm. There was no difference in reduced scattering coefficient (μs') between breast cancer tissue and contra-lateral normal breast (800 nm cancer:9.070±1.217, normal breast;9.348±1.243, p=0.10). The tHb of breast cancer tissue was significantly high, compared with normal breast (cancer:31.0± 14.7, normal breast;21.0±8.2, p&amp;lt;0.001). There was no difference in oxygen saturation (SO2) between breast cancer tissue and contra-lateral normal breast (cancer:72.8±4.1, normal breast;73.8±4.5, p=0.08). Conclusion: Absorption coefficient (μa) and tHb increased in breast cancer, whereas reduced scattering coefficient (μs') did not. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-03.
ABC of Atrial Fibrillation: DIFFERENTIAL DIAGNOSIS OF ATRIAL FIBRILLATION
Authors: G. Y H Lip, R. D S Watson
Journal: BMJ (1995)

LrrI Irr II fElectrocardiogram showing atrial fibrillation with 'fine" f waves.During atrial fibrillation the atrial impulses discharge at a rate of 350-600 per minute, resulting in small (or "fine"), irregular f (fibrillation) waves.The amplitude of these waves varies and may be especially prominent (or "coarse") in lead V1.As only occasional impulses penetrate the atrioventricular node, a totally irregular ventricular rhythm results, which is the characteristic of this arrhythmia.LA I AU {lI ..I LI. 1 J I F .II IF R t 1 fĨ I I . . 5 T W5~~~~~~ĩ e V .P e 41X 11 t 1, iW W I -I I * _ Z
Increased arterial oxygen content -- an important compensatory mechanism in chronic moderate heart failure
Authors: B. Herrlin, C. Sylven
Journal: Cardiovascular Research (1991)

Study objective – The aim was to determine whether mere is a compensatory increase in arterial oxygen content to a hypokinetic circulation in ambulant patients with chronic moderate heart failure caused by dilated cardiomyopathy. Design – Central haemodynamics, arterial oxygen content, arterial haemoglobin concentration, arterial oxygen saturation, and blood gases were measured during a 6 min supine exercise test on a symptom related submaximal workload. At rest, total body haemoglobin was determined. Patients – 19 patients with chronic stable moderate heart failure caused by dilated cardiomyopathy, treated with diuretics and digoxin, were studied. Measurements and main results – During exercise arterial oxygen content correlated inversely with the cardiac index (r = 0.66, p<0.01). The two determinants of arterial oxygen content, arterial haemoglobin concentration and arterial oxygen saturation, also correlated inversely with the cardiac index (r = 0.60, p<0.01 and r = 0.70, p<0.001 respectively). Cardiac index during exercise correlated inversely with total body haemoglobin (r = 0.73, p<0.001). Conclusions – A hypokinetic circulation during daily living induces an increase in arterial oxygen content in patients with chronic stable moderate heart failure caused by dilated cardiomyopathy. Renal hypoperfusion may play a role in stimulating the erythropoiesis and exertional hyperventilation in raising arterial oxygen saturation.
Can poorly performing doctors blame their assessment tools?
Authors: Richard Baker
Journal: BMJ (2005)

In the health services of the Western world, a search is under way to find effective and practical methods for assessing the performance of doctors. Regulators want to identify those doctors with unacceptable performance, educators want methods to guide their various interventions, and managers want information for monitoring and appraisal. Use of multisource feedback (sometimes called 360° feedback) is relatively new in health care, although it has been used in the commercial world for a decade or more. The paediatricians in Sheffield who used SPRAT are being followed by doctors in different disciplines using similar instruments.1 In the United Kingdom, the …
Vaccinating against<i>Helicobacter pylori</i>in the developing world
Authors: Shamila Zawahir, Steven J Czinn, John G Nedrud, Thomas G Blanchard
Journal: Gut Microbes (2013)

Helicobacter pylori infects more than half the world's population and in developing nations the incidence can be over 90%. The morbidity and mortality associated with H. pylori-associated diseases including ulcers and gastric cancer therefore, disproportionately impact the developing world. Mice have been used extensively to demonstrate the feasibility of developing a vaccine for H. pylori infection, and for testing antigens, routes of immunization, dose, and adjuvants. These successes however, have not translated well in clinical trials. Although there are examples where immune responses have been activated, there are few instances of achieving a reduced bacterial load. In vivo and in vitro analyses in both mice and humans demonstrates that the host responds to H. pylori infection through the activation of immunoregulatory mechanisms designed to suppress the anti-H. pylori response. Improved vaccine efficacy therefore, will require the inclusion of factors that over-ride or re-program these immunoregulatory rersponse mechanisms.
On the use of tritium-labelled albumin for studies of intestinal absorption
Authors: K. N. Jeejeebhoy, J. H. Stewart, E. A. Evans, C. C. Booth
Journal: Gut (1964)

Human serum albumin has been successfully labelled with tritium. It is considerably denatured in the process and has a shorter half life when given intravenously than <sup>131</sup>I-labelled albumin. Nevertheless it is satisfactory for absorption studies, although not for turnover observations. These studies on absorption in control subjects and in patients with intestinal malabsorption indicate that the excreted radioactivity may have been derived from endogenous sources rather than from the results of malabsorption alone.