tbuckley/cabot-search huggingface dataset:
CLINICAL REPORT OF A CASE OF PEMPHIGUS VEGETANS
Authors: W. J. RUTHERFURD
Journal: British Journal of Dermatology (1910)

PEMPHIGUS vegetans is one of the most unfamiliar and also one of the rarest of maladies, occuring as it does with even less frequency than once in a hundred and four thousand unselected cases of illness such as are met with in general practice (the figures, so far as statistics of frequency are available, appear t o be 1 in 104,625 cases).It is thus
Can Postmarketing Surveillance Help to Effect Optimal Drug Therapy?
Authors: Brian L. Strom
Journal: JAMA (1979)

Postmarketing drug surveillance (PMS) assesses the epidemiology of drug use and monitors beneficial or harmful effects of drugs following marketing. If used systematically, PMS can substantially improve drug therapy in the United States. This can be accomplished by generating information on drug use and effects otherwise unavailable, by enabling a more efficient drug approval process, and by educating drug prescribers. However, to be successful, any PMS system will need a good deal of input from such prescribers.
Antiphospholipid antibodies are directed against epitopes of oxidized phospholipids. Recognition of cardiolipin by monoclonal antibodies to epitopes of oxidized low density lipoprotein.
Authors: S Hörkkö, E Miller, E Dudl, P Reaven, L K Curtiss, N J Zvaifler, R Terkeltaub, S S Pierangeli, D W Branch, W Palinski, J L Witztum
Journal: Journal of Clinical Investigation (1996)

The optimal clinical management of patients with antiphospholipid antibody syndrome (APS) is uncertain because of a lack of an underlying hypothesis to explain why antiphospholipid autoantibodies (aPL) form to such ubiquitous compounds as phospholipids (PL). In this paper, we demonstrate that many, if not most, aPL are actually directed at neoepitopes of oxidized PL, or neoepitopes generated by adduct formation between breakdown products of oxidized PL and associated proteins. Each cardiolipin (CL) molecule contains four unsaturated fatty acids and is highly susceptible to oxidation, particularly upon exposure to air. Yet, standard anticardiolipin antibodies (aCL) immunoassays routinely bind CL to microtiter wells by evaporation of the ethanol solvent overnight at 4 degrees C. Using a variety of techniques, we demonstrated that rapid oxidation occurs when CL is plated and exposed to air. Sera from apo E-deficient mice, which have high autoantibody titers to oxidized low density lipoprotein, showed a striking time-dependent increase in binding to CL that was exposed to air for increasing periods of time. Monoclonal antibodies to oxidized LDL, cloned from the apo E-deficient mice, also bound to oxidized CL. Both sera and affinity-purified aCL-IgG from APS patients bound to CL progressively as it was oxidized. However, the monoclonal antibodies from apo E-deficient mice, or sera or aCL-IgG from APS patients did not bind to a reduced CL analog that was unable to undergo peroxidation. These data demonstrate that many aPL are directed at neoepitopes of oxidized phospholipids, and suggest that oxidative events may be important in the pathophysiology of APS. In turn, this suggests new therapeutic strategies, possibly including intensive antioxidant therapy.
Epidermal Growth Factor Receptor–Targeted Immunoliposomes Significantly Enhance the Efficacy of Multiple Anticancer Drugs <i>In vivo</i>
Authors: Christoph Mamot, Daryl C. Drummond, Charles O. Noble, Verena Kallab, Zexiong Guo, Keelung Hong, Dmitri B. Kirpotin, John W. Park
Journal: Cancer Research (2005)

Abstract We previously reported the development of epidermal growth factor receptor (EGFR)–targeted immunoliposomes that bind and internalize in tumor cells which overexpress EGFR and/or mutant EGFR variant III (EGFRvIII), enabling intracellular delivery of potent anticancer agents in vitro. We now describe in vivo proof-of-concept for this approach for the delivery of multiple anticancer drugs in EGFR-overexpressing tumor models. Anti-EGFR immunoliposomes were constructed modularly with Fab′ fragments of cetuximab (IMC-C225), covalently linked to liposomes containing probes and/or anticancer drugs. Pharmacokinetic and biodistribution studies confirmed long circulation times (t1/2 = 21 hours) and efficient accumulation in tumors (up to 15% ID/g) irrespective of the presence of the targeting ligand. Although total accumulations of anti-EGFR immunoliposomes and nontargeted liposomes in EGFR-overexpressing tumors were comparable, only immunoliposomes internalized extensively within tumor cells (92% of analyzed cells versus &amp;lt;5% for nontargeted liposomes), indicating different mechanisms of delivery at the cellular level. In vivo therapy studies in a series of xenograft models featuring overexpression of EGFR and/or EGFRvIII showed the superiority of immunoliposomal delivery of encapsulated drugs, which included doxorubicin, epirubicin, and vinorelbine. For each of these drugs, anti-EGFR immunoliposome delivery showed significant antitumor effects and was significantly superior to all other treatments, including the corresponding free or liposomal drug (P &amp;lt; 0.001-0.003). We conclude that anti-EGFR immunoliposomes provide efficient and targeted drug delivery of anticancer compounds and may represent a useful new treatment approach for tumors that overexpress the EGFR. (Cancer Res 2005; 65(24): 11631-8)
Regulation of the human immune response to HBsAg: Effects of antibodies and antigen conformation in the stimulation of helper T cells by HBsAg
Authors: Esteban Celis, Ikunoshin Kato, Richard W. Miller, Tse Wen Chang
Journal: Hepatology (1985)

The role of accessory cells (antigen-presenting cells) in binding HBsAg in the response of human T cells to this antigen was studied. Antibodies to HBsAg of IgG class increased significantly the amount of HBsAg that was captured and internalized by accessory cells in vitro. On the other hand, antibodies to HBsAg of IgM class or the F(ab-)2 and Fab fragments of antibodies to HBsAg of IgG class did not modify the amount of HBsAg associated to these cells. HBsAg that was subjected to various denaturing treatments (acid, organic solvents, urea and heat) was compared for its capacity to react with antibody to HBsAg and stimulate the response of helper T lymphocytes. Results presented here indicate that HBsAg denatured by treatment with formic acid was captured by accessory cells and presented to the T cells much more efficiently than the native HBsAg. These results suggest that the response of helper T lymphocytes to some antigens such as HBsAg can be affected greatly by the presence of antibodies or the antigens- conformation.
Gallbladder Ejection Fraction
Authors: ANTHONY N. KALLOO, SAMUEL SOSTRE, GARY E. MEYERROSE, PANKAJ J. PASRICHA, ZSOLT SZABO
Journal: Clinical Nuclear Medicine (1994)

Thirty consecutive patients with intact gallbladders and biliary pain were evaluated to determine whether gallbladder ejection fraction could identify sphincter of Oddi dysfunction. The mean gallbladder ejection fraction was 45% in patients with abdominal pain and 72% in normal controls. Gallbladder ejection fractions were then correlated with endoscopically measured sphincter of Oddi pressures in patients with abdominal pain. The mean gallbladder ejection fraction was 41% in 7 patients with elevated sphincter pressures and 46% in 23 patients with normal pressures (P = NS). Thirty-six percent of patients with elevated pressures and 33% of patients with normal pressures had abnormal gallbladder ejection fractions. Gallbladder ejection fraction had a sensitivity of 33%, a specificity of 63%, and a positive predictive value of 25% for detection of elevated pressures. Regression analysis revealed a poor correlation between sphincter pressure and gallbladder ejection fraction (r2 = 0.02). These findings suggest that gallbladder ejection fraction cannot be used to diagnose sphincter of Oddi dysfunction in patients before they undergo cholecystectomy.
Selection of Spermatozoa with Normal Nuclei to Improve the Pregnancy Rate with Intracytoplasmic Sperm Injection
Authors: Benjamin Bartoov, Arie Berkovitz, Fina Eltes
Journal: New England Journal of Medicine (2001)

To the Editor: Accurate identification of phenotype is critical for precise genetic characterization.Standard textbooks define the Wolff-Parkinson-White syndrome as the combination of a short PR interval, an increased duration of the QRS complex caused by an initial slow deflection (delta wave), and supraventricular tachyarrhythmias. 1,2 The phenotype identified by Gollob et al. (June 14 issue) 3 is based on "a short PR interval (<120 msec) with a widened QRS complex (>110 msec) or an abnormal initial QRS vector (a delta wave)."Failure to specify that the widened QRS complex must be due to the slow initial delta wave and failure to require the presence of supraventricular arrhythmias result in a much looser definition.No data on the sensitivity or specificity of this definition are provided.Ventricular preexcitation may be intermittent; therefore, the sensitivity is less than 100 percent.The specificity is likely to be very low in this study because of the unusually high incidence of disorders that cause QRS abnormalities in the two families.In contrast, observations in a previous study of familial Wolff-Parkinson-White syndrome showed that structural changes were rare. 4 Most surprising is the fact that complete atrioventricular block, which would require loss of conduction over both normal and accessory pathways, developed in several affected persons.Finally, electrophysiological studies were performed in only eight patients, and several of these studies demonstrated atypical features. 2Therefore, the accuracy of the Wolff-Parkinson-White syndrome phenotype in this study is uncertain, and this may account for the difficulty in linking the physiological function of the identified gene product with the development of the Wolff-Parkinson-White syndrome.
The role of interferon in the protective effect of a synthetic double-stranded polyribonucleotide against intranasal vesicular stomatitis virus challenge in mice
Authors: Erik De Clerco, Marc R. Nuwer, Thomas C. Merigan
Journal: Journal of Clinical Investigation (1970)

Intravenous injection of polyinosinic acid/polycytidylic acid [(poly rI).(poly rC)] offered significant protection against intranasal challenge of young mice with vesicular stomatitis virus (VSV). Optimal protection was obtained when a single dose was administered 2 hr before virus challenge, but repeated doses were effective when started as late as 3 days after virus challenge. The therapeutic ratio or ratio of maximum tolerated dose to minimum effective dose for a single intravenous injection of (poly rI).(poly rC) 2 hr before virus inoculation was >/=8 mg/kg:0.004 mg/kg or >/=200.Dose-response curves for interferon production and antiviral protection by (poly rI).(poly rC) were closely parallel. Equivalent doses of poly rI or poly rC alone did not exert any interferon-inducing capacity or protective effect on intranasal VSV challenge. Several factors, which are known to potentiate or antagonize interferon production, increased or decreased the interferon-inducing capacity and antiviral protection of either (poly rI).(poly rC) or maleic acid/divinyl ether copolymer (MA/DVE) in parallel. Interferon production and antiviral protection by MA/DVE were enhanced by arginine but abolished by prior treatment with MA/DVE; DEAE-dextran (intraperitoneally), kinetin riboside and isopentenyladenosine, and prior injection of endotoxin reduced both interferon production and antiviral protection by (poly rI).(poly rC). Treatment with exogenous interferon in amounts which closely mimicked the levels of circulating interferon produced endogenously by an effective dose of (poly rI).(poly rC) gave protection against intranasal VSV which was identical with that dose of (poly rI).(poly rC). This strongly suggests that interferon production accounts for the whole protective effect of (poly rI).(poly rC) in the intranasal VSV assay.
A delta F508 mutation in mouse cystic fibrosis transmembrane conductance regulator results in a temperature-sensitive processing defect in vivo.
Authors: P J French, J H van Doorninck, R H Peters, E Verbeek, N A Ameen, C R Marino, H R de Jonge, J Bijman, B J Scholte
Journal: Journal of Clinical Investigation (1996)

The most prevalent mutation (delta F508) in cystic fibrosis patients inhibits maturation and transfer to the plasma membrane of the mutant cystic fibrosis transmembrane conductance regulator (CFTR). We have analyzed the properties of a delta F508 CFTR mouse model, which we described recently. We show that the mRNA levels of mutant CFTR are normal in all tissues examined. Therefore the reduced mRNA levels reported in two similar models may be related to their intronic transcription units. Maturation of mutant CFTR was greatly reduced in freshly excised oviduct, compared with normal. Accumulation of mutant CFTR antigen in the apical region of jejunum crypt enterocytes was not observed, in contrast to normal mice. In cultured gallbladder epithelial cells from delta F508 mice, CFTR chloride channel activity could be detected at only two percent of the normal frequency. However, in mutant cells that were grown at reduced temperature the channel frequency increased to over sixteen percent of the normal level at that temperature. The biophysical characteristics of the mutant channel were not significantly different from normal. In homozygous delta F508 mice we did not observe a significant effect of genetic background on the level of residual chloride channel activity, as determined by the size of the forskolin response in Ussing chamber experiments. Our data show that like its human homologue, mouse delta F508-CFTR is a temperature sensitive processing mutant. The delta F508 mouse is therefore a valid in vivo model of human delta F508-CFTR. It may help us to elucidate the processing pathways of complex membrane proteins. Moreover, it may facilitate the discovery of new approaches towards therapy of cystic fibrosis.
Management and in-hospital outcome for patients with acute myocardial infarction in contemporary practice: Japan Acute Myocardial Infarction (JAMI) study— Prospective multicenter observational cohort study in Japan
Authors: Hirotaka Kimura, Hiroshi Kasanuki, Jun-ichi Yamaguchi, Masahiro Yagi, Shinya Fujii, Hiroshi Koganei, Yasuhiro Ishii
Journal: Journal of the American College of Cardiology (2003)
STAFFORDSHIRE BRAHCN: RECENT LEGISLATION AND THE MEDICAL PROFESSION
Authors: J. Russell
Journal: BMJ (1914)

Tlo 67 sojourn on the earth extends to thousands or to millions of years., Tllen there are the still miore interesting -iossibilities of tlhe future, viewed from the evolutionary standpoint.-Willtlle seense of smel1, which: is ahleady on the wane, dis- appear?And will it be replaced-.bysome otlher sense which the exigencies of tthe time may demand?Witlh the rapid cihanges in our modes.ofprogression will the present form of legs continue to be necessary, or will they even- tLually give place to some more useful extremities, such, for
Information and Participation Preferences Among Cancer Patients
Authors: BARRIE R. CASSILETH
Journal: Annals of Internal Medicine (1980)

The present study explored the degree to which patients prefer to become informed about and to participate in their medical care. A total of 256 cancer patients completed an Information Styles Questionnaire and the Beck Hopelessness Scale. Patients' behavior and beliefs were found to incorporate the contemporary standard of informed and active involvement. Significant age trends were found: The younger the patients, the more closely they conformed to the well-informed participant standard of patient behavior; the older the patients, the more likely they were to prefer the older, nonparticipatory patient role. Patients who wanted to be involved in treatment decisions were significantly more hopeful than others. Most patients in each age group displayed high levels of hope, preferences for open communication about their illness, and a desire for maximum amounts of information.
Sustained activation of vascular cells and leukocytes in the rabbit aorta after balloon injury.
Authors: H Tanaka, G K Sukhova, S J Swanson, S K Clinton, P Ganz, M I Cybulsky, P Libby
Journal: Circulation (1993)

BACKGROUND To improve understanding of the cellular basis of the arterial response to injury, we tested whether balloon withdrawal can induce certain inflammatory functions of vascular cells and leukocytes and whether such "activation" persists even after the acute phase of injury. METHODS AND RESULTS We examined the expression of several inducible cell surface molecules in the rabbit aorta at 2, 5, 10, and 30 days after balloon injury. Longitudinal sections encompassing parts of the uninjured, border, and injured zones were examined for expression of vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), class II major histocompatibility (MHC) antigens, and markers for smooth muscle cells (SMCs), macrophages, endothelial cells, and T-lymphocytes. Endothelial cell healing involved true endothelial regeneration as well as migration, as shown by nuclear incorporation of bromodeoxyuridine. Luminal endothelial cells at the leading edge of repopulation at each time point expressed VCAM-1. As healing progressed, VCAM-1 expression decreased in the regenerated endothelial cells. The neointimal endothelium also expressed high levels of ICAM-1 that persisted longer than the elevation of VCAM-1. SMCs in the neointima also showed increased levels of ICAM-1. Some neointimal endothelial cells, SMCs, and macrophages also expressed high levels of class II MHC antigens during 30 days after injury. CONCLUSIONS Local inflammatory activation of endothelial cells, SMCs, and leukocytes occurs in a predictable sequence and persists up to 30 days after balloon injury to the rabbit aorta. Our findings suggest that ongoing local signals persisting after the original balloon injury may contribute to later phases of intimal thickening.
Circus movement atrial flutter in canine sterile pericarditis model. Activation patterns during entrainment and termination of single-loop reentry in vivo.
Authors: W Schoels, M Restivo, E B Caref, W B Gough, N el-Sherif
Journal: Circulation (1991)

BACKGROUND Recently, we used a custom designed "jacket" electrode with 127 bipolar electrodes in a flexible nylon matrix to map the total atrial epicardial surface in the in situ canine heart. Atrial flutter in dogs with sterile pericarditis was shown to be due to a single wave front circulating around a combined functional/anatomic obstacle, with the arc of functional conduction block contiguous with one or more of the atrial vessels. METHODS AND RESULTS In the present study, this model was used to analyze the activation pattern during pacing-induced entrainment and termination of single reentrant loops in a syncytium without anatomically predetermined pathways. Sustained atrial flutter was induced in five dogs with 3-5-day-old sterile pericarditis. Atrial pacing at a cycle length 5-30 msec shorter than the spontaneous cycle length entrained the arrhythmia and could result in a "classical" activation pattern, characterized by an antidromic stimulated wave that collided with the reentrant orthodromic wave front of the previous beat at a constant site. However, two variations of this classical activation pattern were also observed: 1) Pacing at short cycle lengths could lead to localized conduction block in antidromic direction, forcing a change in the pathway of the antidromic wave front. This could prevent the expected shift of the site of collision in antidromic direction. 2) The stimulated orthodromic wave front could also use a pathway different from that of the original reentrant impulse, so that a different circuit was active during the pacing period. Termination of atrial flutter by rapid atrial stimulation was associated with progressive slowing and finally blocking of the paced orthodromic wave front and a progressive shift of the site of collision in antidromic direction. The occurrence of conduction block was determined by the cycle length of stimulation and the number of stimulated beats. A longer train at the critical cycle length or the critical number of beats at a shorter cycle length could reinduce the same reentrant circuit or a different reentrant circuit, respectively, during stimulated cycles following the beat that terminated reentry. CONCLUSIONS The epicardial activation sequence during entrainment of reentrant arrhythmias does not necessarily follow a standard activation pattern. Instead, the stimulated orthodromic as well as the antidromic wave front might use a pathway different from that of the original reentrant wave front. The mechanisms of termination, failure of termination, and reinitiation of single-loop reentry are similar to those in the "figure-eight" reentrant circuit.
Overexpression of Endothelial Nitric Oxide Synthase Prevents Diet-Induced Obesity and Regulates Adipocyte Phenotype
Authors: Brian E. Sansbury, Timothy D. Cummins, Yunan Tang, Jason Hellmann, Candice R. Holden, Matthew A. Harbeson, Yang Chen, Rakesh P. Patel, Matthew Spite, Aruni Bhatnagar, Bradford G. Hill
Journal: Circulation Research (2012)

Endothelial dysfunction is a characteristic feature of diabetes and obesity in animal models and humans. Deficits in nitric oxide production by endothelial nitric oxide synthase (eNOS) are associated with insulin resistance, which is exacerbated by high-fat diet. Nevertheless, the metabolic effects of increasing eNOS levels have not been studied.The current study was designed to test whether overexpression of eNOS would prevent diet-induced obesity and insulin resistance.In db/db mice and in high-fat diet-fed wild-type C57BL/6J mice, the abundance of eNOS protein in adipose tissue was decreased without significant changes in eNOS levels in skeletal muscle or aorta. Mice overexpressing eNOS (eNOS transgenic mice) were resistant to diet-induced obesity and hyperinsulinemia, although systemic glucose intolerance remained largely unaffected. In comparison with wild-type mice, high-fat diet-fed eNOS transgenic mice displayed a higher metabolic rate and attenuated hypertrophy of white adipocytes. Overexpression of eNOS did not affect food consumption or diet-induced changes in plasma cholesterol or leptin levels, yet plasma triglycerides and fatty acids were decreased. Metabolomic analysis of adipose tissue indicated that eNOS overexpression primarily affected amino acid and lipid metabolism; subpathway analysis suggested changes in fatty acid oxidation. In agreement with these findings, adipose tissue from eNOS transgenic mice showed higher levels of PPAR-α and PPAR-γ gene expression, elevated abundance of mitochondrial proteins, and a higher rate of oxygen consumption.These findings demonstrate that increased eNOS activity prevents the obesogenic effects of high-fat diet without affecting systemic insulin resistance, in part, by stimulating metabolic activity in adipose tissue.