tbuckley/cabot-search huggingface dataset:
HOMEOSTASIS OF ANTIBODY FORMATION IN THE ADULT RAT
Authors: Donald A. Rowley, Frank W. Fitch
Journal: The Journal of Experimental Medicine (1964)

Passive immunization of rats with homologous anti-sheep erythrocyte serum markedly inhibited the primary antibody response to various doses of sheep erythrocytes. Inhibition was "specific" and apparently produced by either "19S" or "7S" antibody to the antigen. Passive immunization inhibited splenic hyperplasia associated with the primary antibody response. Passive immunization 24 hours after active immunization effectively inhibited the primary antibody response. The markedly suppressive effect of specific antibody on the primary antibody response contrasted sharply with the absence of this effect on the secondary response. Antigen-antibody complexes formed in vitro elicited no measurable primary antibody response but did elicit a high secondary response. Exposure of normal spleen cells to the antibody in vivo or in vitro suppressed their response to the antigen in x-irradiated recipients. In contrast, cells from previously immunized animals transferred to x-irradiated animals produced antibody in the presence of passively given antibody. Thus, "potential antibody-forming cells" from normal animals were unresponsive to the antigen in the presence of specific antibody, while "antibody-forming cells" from previously immunized animals responded to the antigen in the presence of antibody. Presumably, antibody actively produced in small quantities by a few antibody-forming cells might inhibit antibody formation by potential antibody-forming cells. Confirmation of this suggestion was obtained by showing that some animals initially injected with small doses of antigen failed to produce measurable antibody to subsequent injections of larger doses of the antigen. Low doses of antigen capable of inducing unresponsiveness produced no measurable circulating antibody, but these doses did produce increased numbers of plaque-forming (antibody-releasing) cells in spleens of rats. Thus, the formation of specific antibody may provide a homeostatic or "feed-back" mechanism which controls or limits production of specific antibody to the portion of the antibody-forming system previously stimulated by the antigen. This mechanism may account in part for immunological unresponsiveness produced in certain other related experimental systems.
Hemothorax as a Complication of Anticoagulant Therapy in the Presence of Pulmonary Infarction
Authors: Harvey B. Simon
Journal: JAMA (1969)

Two elderly women had hemothorax as a complication of anticoagulant therapy for pulmonary infarction. To our knowledge, this complication has not previously been reported. Both patients were treated with heparin sodium and warfarin sodium following pulmonary infarction. Excess anticoagulant effect developed in both, and both had significant intrapleural hemorrhage, which was fatal in one case. Clinical differentiation between simple pulmonary emboli and emboli with infarction is difficult but important.
Acute Metabolic Response to High-Carbohydrate, High-Starch Meals Compared With Moderate-Carbohydrate, Low-Starch Meals in Subjects With Type 2 Diabetes
Authors: Mary C Gannon, Frank Q Nuttall, Sydney A Westphal, Sean Fang, Nacide Ercan-Fang
Journal: Diabetes Care (1998)

The monosaccharides resulting from the digestion of ingested carbohydrates are glucose, fructose, and galactose. Of these three monosaccharides, only ingested glucose resulted in a large increase in the plasma glucose concentration. Fructose (Metabolism 41:510-517, 1992) and galactose (Metabolism 42:1560-1567, 1993) had only a minor effect. Therefore, we were interested in determining whether we could design a mixed meal, using foods of known monosaccharide, disaccharide, and starch composition, the ingestion of which would result in only a small rise in plasma glucose concentration.The experimental meal was composed of very little readily digestible starch but rather large amounts of fruits and vegetables. It contained 43% carbohydrate, 22% protein, and 34% fat. The results were compared with a second type of meal that contained 55% carbohydrate, 15% protein, and 30% fat, with an emphasis on complex carbohydrates (starch). It also was compared with a third meal that contained 40% carbohydrate, 20% protein, and 40% fat, typical of that consumed by the average American. The test meals were ingested in random order by people with type 2 diabetes who were not treated with oral hypoglycemic agents or insulin. Each subject ingested each type of meal. The same identical meal was ingested at 0800, 1200, and 1700.The integrated 24-h plasma glucose area response was statistically significantly smaller (P < 0.05) after ingestion of the low-starch meals compared with the high-starch, high-carbohydrate meals or the typical American meals. The 24-h integrated serum insulin area response also was statistically significantly less (P < 0.05) after ingestion of the low-starch meals compared with the high-starch meals or the typical American meals. The serum triglyceride area response was similar after ingestion of all three test diets.A diet in which fruits, nonstarch vegetables, and dairy products are emphasized may be useful for people with type 2 diabetes.
PK modulation of haptenylated peptides via non-covalent antibody complexation
Authors: Eike Hoffmann, Anish Konkar, Sebastian Dziadek, Hans-Peter Josel, Karin Conde-Knape, Holger Kropp, Lothar Kling, Kay Stubenrauch, Irmgard Thorey, Stefan Dengl, Ulrich Brinkmann
Journal: Journal of Controlled Release (2013)

We applied noncovalent complexes of digoxigenin (Dig) binding antibodies with digoxigeninylated peptide derivatives to modulate their pharmacokinetic properties. A peptide derivative which activates the Y2R receptor was selectively mono-digoxigeninylated by reacting a NHS-Dig derivative with an ε-amino group of lysine 2. This position tolerates modifications without destroying receptor binding and functionality of the peptide. Dig-peptide derivatives can be loaded onto Dig-binding IgGs in a simple and robust reaction, thereby generating peptide-IgG complexes in a defined two to one molar ratio. This indicates that each antibody arm becomes occupied by one haptenylated peptide. In vitro receptor binding and signaling assays showed that Dig-peptides as well as the peptide-antibody complexes retain better potency than the corresponding pegylated peptides. In vivo analyses revealed prolonged serum half-life of antibody-complexed peptides compared to unmodified peptides. Thus, complexes are of sufficient stability for PK modulation. We observed more prolonged weight reduction in a murine diet-induced obesity (DIO) model with antibody-complexed peptides compared to unmodified peptides. We conclude that antibody-hapten complexation can be applied to modulate the PK of haptenylated peptides and in consequence improve the therapeutic efficacy of therapeutic peptides.
Cell-mediated immunity in acute and chronic hepatitis.
Authors: J R Wands, J L Perrotto, E Alpert, K J Isselbacher
Journal: Journal of Clinical Investigation (1975)

Peripheral lymphocytes from patients with hepatitis-B surface antigen (HBsAg)-positive and -negative acute hepatitis (AH), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and normal controls were tested for in vitro cytotoxicity and blast transformation. Cytotoxicity was measured by chrominum (21Cr) release into the medium from 51Cr-labeled Chang liver cells after incubation for 6 h with peripheral lymphocytes at a lymphocyte target cell ratio of 200:1. Concomitant 72-h incubation studies were performed to assess thymus cell-dependent (T) lymphocyte function as measured by conccanavalin A (Con A)- stimulated incorporation of tritiated thymidine (blast transformation) and by cytotoxicity. It was found that (a) lymphocytes from patients with AH are cytotoxic to Chang liver cells compared to controls (P less than 0.001); (b) lymphocytes from patients with acute and chronic hepatitis are less cytotoxic when incubated with autologous and homologous HB2Ag-positive and -negative AH, CAH, and CPH are as cytotoxic as normal controls when stimulated with a nonspecific mitogen such as Con A; and (d) lymphocytes from patients with CAH while on prednisone therapy showed marked depression of cytotoxicity when stimulated with Con A. Thus these studies show that patients with AH have circulating T lymphocytes which are capable of causing the destruction of Chang liver cells. There is no defect in T-cell function as measured by Con A-stimulated cytotoxicity. There is a serum factor (s) in patients with acute and chronic hepatitis which inhibits spontaneous and induced lymphocyte cytotoxicity and blast transformation. Finally, prednisone treatment appears to inhibit lymphocyte cytotoxicity in patients with CAH.
Polypill remains the only panacea in sight for cardiovascular disease, trial organiser says
Authors: N. Hawkes
Journal: BMJ (2012)

In less than a decade since it was proposed, the polypill has been the subject of many studies and remains “the only panacea we can see” for the toll taken by cardiovascular disease, delegates were told at a seminar in London on 13 July.

Denis Xavier is project director and coauthor of the TIPS trial (The Indian Polycap Study) and head of the department of pharmacology at St John’s Medical College in Bangalore. He argued at a seminar organised by C3 Collaborating for Health—an international charity aimed at controlling non-communicable diseases worldwide—that the polypill had demonstrated its safety and efficacy. But several barriers still stood in the way of its wider adoption.

Since Nicholas Wald and Malcolm Law first suggested the idea of combining a statin, three blood pressure lowering drugs, …
705-4 Idiopathic Right Ventricular Outflow Tract Tachycardia: Narrowing the Anatomic Location for Successful Ablation
Authors: Colin Movsowitz, Charles D. Gottlieb, David J. Callans, Josephine R. Saligan, Volker Menz, David Schwartzman, Erica Zado, Francis E. Marchlinskl
Journal: Journal of the American College of Cardiology (1995)
AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial
Authors: Peter A LeWitt, Ali R Rezai, Maureen A Leehey, Steven G Ojemann, Alice W Flaherty, Emad N Eskandar, Sandra K Kostyk, Karen Thomas, Atom Sarkar, Mustafa S Siddiqui, Stephen B Tatter, Jason M Schwalb, Kathleen L Poston, Jaimie M Henderson, Roger M Kurlan, Irene H Richard, Lori Van Meter, Christine V Sapan, Matthew J During, Michael G Kaplitt, Andrew Feigin
Journal: The Lancet Neurology (2011)
EMPLOYMENT OF THE PHYSICALLY HANDICAPPED
Authors: D. L. LYNCH
Journal: JAMA (1941)

The subject of this paper is one that arouses two emotions—one of sympathy, the other of fear—each tempered by the environment in which we find ourselves. When you come on a one-legged young man, sitting sad faced at a busy street corner with cap in hand awaiting your tribute to his incapacity, you pity him. You feel that there should be some way that he could be made self supporting. Your business takes you into the transportation office of a large machinery manufacturing concern where you carry on with a pleasant middle-aged man who uses an artificial larynx to talk with you, and excuses himself while he answers a telephone call. You admire him. Some, at least, of the personnel engaged in vocational rehabilitation and in other social work will say that industry has not given the handicapped a fair break toward employment. On the other hand, when an employer
HLA B27, Yersinia enterocolitica, and ankylosing spondylitis.
Authors: P Pease, J England, R Tyler, P Mackintosh
Journal: Annals of the Rheumatic Diseases (1980)

reduced diffusion capacity had more often higher values of DNA antibody binding capacity, antinuclear anti- bodies, and rheumatoid factor, but these differences were not significant.Similar results are reported by Turner-Warwick.7 Immune complex deposition in lung capil- laries, detected with immunofluorescence methods, are described in only a few cases.8-'0Despite this fact it can be suggested that immunological reaction, for example the deposition of immune complexes, is one of the initial steps in the development of pulmonary manifestations.
OC-021 A Retrospective Audit of Pneumococcal &amp; Influenza Vaccination in Coeliac Disease: Abstract OC-021 Table 1
Authors: J Khan, A Jennings, S Subramanian
Journal: Gut (2013)

<h3>Introduction</h3> Patients with coeliac disease (CD) are at increased risk of mortality from sepsis. In particular, the risk of sepsis with encapsulated organisms such as Pneumococci is higher<sup>1</sup>. This may be a consequence of hyposplenism. Current Department of Health Green Book guidelines as well as Coeliac UK recommend vaccination against Pneumococci and influenza. We aimed to investigate whether or not patients with CD received vaccination against Pneumococci and influenza. <h3>Methods</h3> CD patients were identified through a register of 1000 ICD-10 classified patients currently under follow up at Royal Liverpool and Broadgreen University Hospitals NHS Trust. A random sample of 250 patients was selected from the register. Electronic case notes were interrogated for demographic details as well as the most recently confirmed comorbidities. Patients of all ages were included in the study. Patients aged over 65 and patients with certain comorbidities (e.g. chronic obstructive airways disease, ischaemic heart disease, liver cirrhosis etc) were analysed separately as these patients should already be immunised against pneumococci and influenza regardless of their coeliac disease diagnosis. Immunisation status was obtained by contacting individual patient's general practitioners. The proportion of vaccinated patients were analysed according to the age groups &lt; or &gt; 65. <h3>Results</h3> A total of 250 patients were included out of which we were able to obtain records for 198 patients. Of the 198 patients, 32% of patients had osteopenia and 13% of patients had one or more concurrent autoimmune illness (e.g. thyroid disease, pernicious anaemia, Sjogren's syndrome). 129 patients were &lt; 65 years of age (M: F ratio 1: 2, median age-50, range 19–64) and 69 were &gt; 65 (M: F ratio 1: 2, median age-73, range 65–84). In the &lt; 65 category, we found 10 with no comorbidities necessitating vaccination which left 119 patients in the main study arm; 23 (19.3%) were vaccinated against Pneumococci and 42 (35%) against influenza. <h3>Conclusion</h3> Very few patients with CD are vaccinated against preventable causes of sepsis such as Pneumococci. Gastroenterologists, GPs and patients need to be aware of the increased risk of sepsis and the need to administer vaccines against preventable infections in CD patients. Vaccination status should be routinely obtained during follow up visits. Due to the lack of a simple clinical test for hyposplenism and the high prevalence of hyposplenism in CD, it is worth considering pneumococcal vaccination for all CD patients at diagnosis. <h3>Disclosure of Interest</h3> J. Khan: None Declared, A. Jennings: None Declared, S. Subramanian Speaker bureau with: Shire, Abbott and Dr Falk pharma, Conflict with: Advisory board member for Vifor Pharma and Abbott <h3>Reference</h3> Ludvigsson JF, Olén O, Bell M, Ekbom A, Montgomery SM. Coeliac disease and risk of sepsis. <i>Gut</i> 2008; 57(8):1074–80.
Abstract 4713: Stent Degradation of Novel Fully Bioabsorbable Salicylate-Based Sirolimus-Eluting Stent: Assessment by Optical Coherence Tomography in Pig Coronary Artery
Authors: Daisuke Matsumoto, Toshiro Shinke, Sarah Geva, Nicolas Chronos, Keith Robinson, Refat Jabara
Journal: Circulation (2009)
Drug company takes 10 others to court for patent infringement
Authors: C. Kovac
Journal: BMJ (2001)

Richter Gedeon, Hungary's largest pharmaceutical firm, has filed a patent infringement suit in the US district court in New York against 10 international drug manufacturers for violating five of Richter Gedeon's registered patents.

The suit alleges that the companies, all of which do business in the United States, unlawfully use Richter Gedeon's patented crystallised polymorph version of famotidine, an ingredient used in antiulcer drugs. …
Tissue-Type Plasminogen Activator Therapy Versus Primary Coronary Angioplasty: Impact on Myocardial Tissue Perfusion and Regional Function 1 Month After Uncomplicated Myocardial Infarction
Authors: Luciano Agati, Paolo Voci, Patrick Hickle, Dario C. Vizza, Camillo Autore, Francesco Fedele, Steven B. Feinstein, Armando Dagianti
Journal: Journal of the American College of Cardiology (1998)
Prolactin in anorexia nervosa.
Authors: A J Isaacs, D Leslie, J Gomez, P R Raggatt
Journal: BMJ (1977)

group as a whole (P <0 025).The antipyrine half life of the 20 non-deficient people was 11 3±2-1 h, which was significantly shorter than in either the group as a whole (P < 0-05) or the 16 people with low vitamin levels (P< 0001).We conclude that poor nutrition in the elderly is at least in part responsible for the decline in microsomal enzyme function with age.
Intraluminal force transducer measurements of human oesophageal peristalsis
Authors: C. E. Pope, P. F. Horton
Journal: Gut (1972)

A force transducer has been developed to measure peristaltic propulsive force (;pull') in the oesophagus. Utilizing a mercury-in-Silastic strain gauge to which a sphere has been attached, this transducer can be calibrated to measure value for force, work, and power. Variability in force values were found between different peristaltic waves at the same site, between different sites in the same subject, and between different control subjects. Control subjects' patterns did not change when the subjects were studied on separate occasions. Patients complaining of dysphagia, who had normal radiographs and manometric tracings, revealed force values that were significantly different from control values. This device should prove useful in the quantitation of oesophageal muscle function.
Hepatitis C viremia in patients with hepatitis C virus infection
Authors: Anna S.F. Lok, Ramsey Cheung, Rachel Chan, Vincent Liu
Journal: Hepatology (1992)

Sera from 103 patients were tested for hepatitis C virus RNA by nested polymerase chain reaction assay. Using primers from the highly conserved 5′untranslated region, we detected hepatitis C virus RNA in 67 (88.2%) of 76 patients positive for antibody to hepatitis C virus by both second–generation and neutralization enzyme immunoassays. Hepatitis C virus RNA was detected in 93% of patients who had been infected for 10 yr or less and in 89% of those who had been infected for longer than 10 yr. Hepatitis C virus RNA was detected in all patients with chronic hepatitis, active cirrhosis or hepatocellular carcinoma and in 50% of those with nonspecific reactive hepatitis or inactive cirrhosis. Hepatitis C virus RNA was not detected in sera from 22 patients negative for antibody to hepatitis C virus or in 5 patients positive for antibody to hepatitis C virus by second–generation but not by neutralization enzyme immunoassay. Using primers from the less conserved nonstructural region 4, we detected hepatitis C virus RNA at a lower frequency, in 66% of patients who were positive for antibody to hepatitis C virus by both secondgeneration and neutralization enzyme immunoassays. The detection rate was higher in patients with frequent parenteral exposure. Our study showed that hepatitis C viremia can be detected in most patients with hepatitis C virus infection, including those with long–standing infection or advanced liver disease. (Hepatology 1992;15:1007-1012).
Discordant Bone Scan and Gallium-67 Scan Findings in Bone Metastasis
Authors: BHARTI R. PATEL
Journal: Clinical Nuclear Medicine (1985)

A 48-year-old white man was admitted to the hospital with severe back pain and pain in the right groin region. The patient had undergone a left pneumonectomy approximately four months prior to admission. At that time, the patient had experienced some degree of discomfort in his back. His preoperative chest x-rays, lumbosacral x-rays, and bone scan revealed no evidence of bone metastasis. Presently, because of the severe back pain, he was admitted to the hospital for his workup. Serum alkaline phosphatase level was 101U,and LDH level was 159U. Chest x-ray, lumbosacral x-rays, and bone scan did not reveal any bone metastasis. Because of the severe pain, a Ga-67 scan was performed for further evaluation. Areas of increased activity in lumbar-1 vertebra, left sacroiliac joint region, and right acetabular region were noted. Discordant bone scan and Ga-67 scan findings in bone metastases were found. On both the occasions, the bone scans were performed using Tc-99m MDP. Because of positive Ga-67 scan finding, a bone biopsy of an abnormally increased activity in lumbar-1 vertebra was obtained. The histopathological examination confirmed the lesion to be metastasis from patient's bronchogenic carcinoma. Thus, this patient's bone metastasis could be detected on Ga-67 scan when a bone scan failed to detect those bone metastasis.
What is stopping the NHS from using bevacizumab for macular degeneration and other retinal disorders?
Authors: A. Lotery, C. MacEwen
Journal: BMJ (2014)

Government must act to remove the hurdles

Age related macular degeneration (AMD) is the commonest cause of blindness among elderly people in the developed world.1 The treatment of neovascular AMD was revolutionised by clinical trials of ranibizumab (Lucentis), a monoclonal antibody against vascular endothelial growth factor. These showed that vision was improved with repeated monthly intravitreal injections.1 The National Institute for Health and Care Excellence (NICE) approved its use in 2008 and subsequently approved aflibercept, which also inhibits vascular endothelial growth factor, in 2013.

Since then, carefully conducted clinical trials have shown that a similar drug, bevacizumab (Avastin), is as effective as ranibizumab at improving or stabilising vision in patients with neovascular AMD. The two largest studies are CATT (Comparison of AMD Treatments Trials) in the US2 and the IVAN (Inhibition of VEGF in Age-related Choroidal Neovascularisation) trial in the UK.3 Bevacizumab, however, is not licensed for use in eyes.

There are concerns that bevacizumab is not as safe as ranibizumab. However, a recent Cochrane review found no difference between the two drugs for deaths, all serious systemic adverse events, or specific subsets of adverse events with the exception of gastrointestinal disorders.4 It concluded that, from a safety point of view, …
Vegetable consumption and acute appendicitis
Authors: R Flowerdew, A C Gatrell, A A Lovett
Journal: BMJ (1986)

Recurrence of focal glomeruloscierosis despite cyclosporin treatment after renal transplantation SIR,-Professor Alain Meyrier and colleagues ( 22March, p 789) repprted the remission of the idiopathic nephrotic syndrome after cyclosporin therapy.While the remission was total in the three patients with minimal change nephropathy, it was only partial in the three others with focal glomerulosclerosis.The authors considered the