tbuckley/cabot-search huggingface dataset:
598. In-Vivo Test of Coagulation Factor VIII with Improved Properties for Hemophilia A Gene Therapy by Helper-Dependent Adenoviral Vectors
Authors: Vincenzo Cerullo, Michael McCormack, Racel Garcia, Christian Clarke, Steven W. Pipe, Brendan Lee
Journal: Molecular Therapy (2005)

Top of pageAbstract
Hemophilia A is an X-linked bleeding disorder resulting from a deficiency of coagulation factor VIII (FVIII). FVIII expression is limited by unstable mRNA, interaction with endoplasmic reticulum (ER) chaperones, a requirement for facilitated ER to Golgi transport through interaction with the mannose-binding lectin LMAN1 and the instability of the activated form of FVIII (FVIIIa). Bioengineering strategies, like the development of different variants of recombinant FVIII molecules, by rational design can overcome these limitations.

Helper-dependent adenovirus (HDV) can facilitate transfer of up to 36 kb transgene DNA and is optimal for the study of FVIII and its variants. In this study we evaluated the in vivo efficacy of six different variants of recombinant FVIII. To this end, we generated six different helper dependent adenoviral vectors carrying human cDNA's regulated by the liver tissue restricted PEPCK promoter.

To compare the short term efficacy and duration of hFVIII expression and infectivity of the different HDV hFVIII variants, FVIII deficient mice were treated with each vector at a dose of 5X1012 vp/kg via tail vein injection. Plasma was collected at baseline, two and four weeks post-injection and FVIII biological activity was quantified by Coatest chromogenic bioassay. In this experiment, all vectors expressed functional FVIII at two weeks post-injection. FVIII activity varied from 2-8% in WT FVIII to up to 70% in some other constructs. Functional FVIII activity dropped significantly in all vectors by 4 weeks except in the mice treated with an inactivation resistant rFVIII (HDV IR8 hFVIII) suggesting that variant may exhibit an improved immunological profile. Interestingly, another construct, containing the F309S substitution, which decreases binding to BiP and thus increases the rate of secretion of the FVIII mutation, appears to significantly improve activity over WT hFVIII in vivo.
Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction
Authors: Masaharu Ishihara, Ichiro Inoue, Takuji Kawagoe, Yuji Shimatani, Satoshi Kurisu, Kenji Nishioka, Yasuyuki Kouno, Takashi Umemura, Syuji Nakamura, Hikaru Sato
Journal: Journal of the American College of Cardiology (2001)
Plasma Lipoproteins: Disorders in Their Metabolism.
Authors: Donald S. Fredrickson
Journal: Annals of Internal Medicine (1971)

Meeting Abstracts1 May 1971Plasma Lipoproteins: Disorders in Their Metabolism.Donald S. Fredrickson, M.D., F.A.C.P.Donald S. Fredrickson, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-74-5-843_6 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptLipoproteins have gradually become important in clinical medicine, as markers of new diseases and as models for better understanding of cholesterol and triglyceride metabolism. The internist frequently encounters several types of hyperlipoproteinemia and must be aware of hypolipoproteinemia as a sign of unusual genetic abnormalities, such as abetalipoproteinemia and Tangier disease. The state-of-the-art of both research and application in this area is reviewed.... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Bethesda, Md. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1971Volume 74, Issue 5Page: 843-843KeywordsBiomarkersBlood plasmaCholesterolGenetic diseasesLipoproteins Issue Published: 1 May 1971 PDF downloadLoading ...
Vitamin-B12 Status of Patients on Long-term Metformin Therapy
Authors: G. H. Tomkin, D. R. Hadden, J. A. Weaver, D. A. D. Montgomery
Journal: BMJ (1971)

Vitamin-B(12) malabsorption has been found in 21 (30%) of 71 diabetic patients taking long-term metformin therapy in addition to dietary management. The patients with evidence of B(12) malabsorption had significantly lower haemoglobin levels (and significantly higher serum folic acid levels) than those with normal B(12) absorption. Steatorrhoea was found in only one patient. Stopping metformin therapy resulted in reversion of B(12) absorption to normal in most patients examined. Four patients with B(12) malabsorption were found to have pathologically low serum B(12) levels. The causes and implications of these findings are discussed and it is concluded that all patients on long-term metformin therapy should have annual serum B(12) estimations.
End-tidal CO2 pressure determinants during hemorrhagic shock
Authors: Arnaldo Dubin, Gastón Murias, Elisa Estenssoro, Héctor Canales, Pablo Sottile, Julio Badie, Marcelo Barán, Silvio Rossi, Mercedes Laporte, Fernando Pálizas, Jorge Giampieri, Diego Mediavilla, Esteban Vacca, Diego Botta
Journal: Intensive Care Medicine (2000)
WHO vaccine expert had conflict of interest, Danish newspaper claims
Authors: J. Carlowe
Journal: BMJ (2010)

Controversy has arisen at the World Health Organization after allegations that some WHO experts, including a leading vaccine adviser, have financial ties to the drug industry.

Documents acquired through the Danish Freedom of Information Act by the Danish daily newspaper Information show that Juhani Eskola, a Finnish vaccines adviser on the WHO board, has received £5.6m (€6.2m; $9m) for his research centre, the Finnish National Institute for Health and Welfare. The money, from GlaxoSmithKline for research on vaccines during 2009, is the institute’s main source of income.

Professor Eskola is the deputy director general of the institute …
Chief medical officer calls for rewards to improve clinical practice
Authors: Caroline White
Journal: BMJ (2006)

The chief medical officer for England, Liam Donaldson, has said that financial rewards and penalties could be introduced in a bid to root out unacceptable regional variations in clinical practice.

Professor Donaldson was speaking last week at the launch of the latest issue of his annual report on the state of public health, which draws on data for 2005 from the former 28 strategic health authorities.

He said that despite great improvements in medical education and the growth of an evidence …
Public Long-term Care Insurance in Japan
Authors: Naoki Ikegami
Journal: JAMA (1997)

A public long-term care (LTC) insurance program is likely to be introduced to Japan in the year 2000. A consensus on the need for more LTC resources in the rapidly aging society and dissatisfaction with the current system are some of the factors that have contributed to its introduction. Half the costs will be paid by premiums that will be levied on all those older than 40 years, and half will be covered by general taxation. The insurer will be the municipalities with a pooling mechanism at the national level to balance the differences in their demographic structure. The benefits will include institutional care, respite care, day care, home help, visiting nurses, and loan of devices. Eligibility status will be classified into 6 levels that will be determined by assessment of functional and cognitive status. However, there are few mechanisms to limit benefits and contain costs. Problems also exist in the design of the eligibility classification and in the assessment instrument. The proposed LTC insurance system highlights the need for defining what should be included in a "basic package" of LTC as an entitlement for every citizen, for an organizational mechanism and an assessment instrument to deliver services efficiently and equitably, and for physicians to work outside the traditional medical model. To what degree the Japanese public in general, and physicians in particular, is willing to deal with these issues is a challenge for the 21st century.
THE TREATMENT OF CHRONIC INFLAMMATION OF THE TONSILS.
Authors: J. A. ELLEGOOD
Journal: JAMA (1898)

The brevity of this paper will preclude the consideration of inflammation of the tonsils due to syphilis, tuberculosis, lupus and malignant disease. Chronic amygdalitis is primarily and essentially a chronic disease of the tonsillar crypts, and rational treatment must aim at their destruction or removal. While usually attended with hypertrophy, such is not always the case. The enlargement is often so slight as to be hardly appreciable, and the morbid process is of so low a grade as to present, except at occasional intervals, but few of the usual features of inflammation. Knight has divided hypertrophied tonsils into three groups: 1, those that are decidedly increased in volume and constantly project beyond the palatine arches; 2, flat diffuse tonsils which project but slightly into the fauces except during the act of retching; 3, those that encroach upon the pharyngeal space and yet do not appear beyond the free margin of
In vitro studies on the biologic effects of fibers: correlation with in vivo bioassays.
Authors: B T Mossman
Journal: Environmental Health Perspectives (1990)

In vitro studies employing organ cultures, primary cell cultures, cell lines, and bacterial systems have been used to assess the toxicity, mutagenicity, and carcinogenic potential of asbestos and nonasbestos fibers. These experiments have been useful in defining mechanisms contributing to the causation of fiber-associated lung diseases. Long (greater than 8 microns), thin asbestos fibers are more active in vitro than short (less than or equal to 2 microns) fibers or nonfibrous particles, an observation supporting the importance of fiber dimension in disease. Although in vitro bioassays cannot evaluate characteristics such as clearance and/or durability of fibers which may be critical determinants of fiber toxicity in lung, they can be used both to address dosimetry at the cellular level (i.e., number of fibers per cell that elicit a measurable biologic end point) and to evaluate preventive approaches to fiber-induced cell injury. Development of in vitro models employing target cells of the lung, i.e., mesothelial cells, tracheobronchial epithelial cells, and lung fibroblasts, as well as carefully characterized preparations of fibers and particles, will be necessary to evaluate whether in vitro bioassays are amenable to predicting the pathogenic potential of synthetic and naturally occurring fibers comparatively.
Silent Prostatism
Authors: Joseph B. Dowd
Journal: JAMA (1961)

Sixty-four men who had notably few urinary complaints progressed from bladder neck obstruction to uremia. Contrary to popular belief, they were not neglected, feeble hermits whose senses were obtunded by past excesses or senility. Physicians, their fathers, and clergy comprised one-fifth of this series. Intelligent men often accepted bladder symptoms as "normal acquisitions" of age. The diagnosis was delayed when unsuspecting physicians were misled by the deceptive rectal finding of a "small prostate." Men undergoing abdominoperineal resection are particularly prone to development of silent prostatism. Liberal use of blood urea nitrogen determinations and intravenous pyelograms are advocated in men having even slight evidence of abnormality of the bladder neck. In retrospect, cautious bladder decompression in the hospital is still advised as an initial step in management. Thirty-two men (50 per cent) remained uremic.
Kinetics of Tumor Destruction by Chimeric Antigen Receptor-modified T Cells
Authors: Usanarat Anurathapan, Robert C Chan, Hakeem F Hindi, Roopa Mucharla, Pradip Bajgain, Brendan C Hayes, William E Fisher, Helen E Heslop, Cliona M Rooney, Malcolm K Brenner, Ann M Leen, Juan F Vera
Journal: Molecular Therapy (2013)

The use of chimeric antigen receptor (CAR)-modified T cells as a therapy for hematologic malignancies and solid tumors is becoming more widespread. However, the infusion of a T-cell product targeting a single tumor-associated antigen may lead to target antigen modulation under this selective pressure, with subsequent tumor immune escape. With the purpose of preventing this phenomenon, we have studied the impact of simultaneously targeting two distinct antigens present on tumor cells: namely mucin 1 and prostate stem cell antigen, both of which are expressed in a variety of solid tumors, including pancreatic and prostate cancer. When used individually, CAR T cells directed against either tumor antigen were able to kill target-expressing cancer cells, but tumor heterogeneity led to immune escape. As a combination therapy, we demonstrate superior antitumor effects using both CARs simultaneously, but this was nevertheless insufficient to achieve a complete response. To understand the mechanism of escape, we studied the kinetics of T-cell killing and found that the magnitude of tumor destruction depended not only on the presence of target antigens but also on the intensity of expression-a feature that could be altered by administering epigenetic modulators that upregulated target expression and enhanced CAR T-cell potency.
A Belgian case of the eosinophilia-myalgia syndrome
Authors: J. M. Naeyaert, C. Cuelenaere, J. De Bersaques, D. Platevoet, A. Kint
Journal: British Journal of Dermatology (1991)

Journal Article A Belgian case of the eosinophilia‐myalgia syndrome Get access J. M. Naeyaert, J. M. Naeyaert Department of Dermatology, University Hospital, De Pintelaan 185, 9000 Gent, Belgium Search for other works by this author on: Oxford Academic Google Scholar C. Cuelenaere, C. Cuelenaere Department of Dermatology, University Hospital, De Pintelaan 185, 9000 Gent, Belgium Search for other works by this author on: Oxford Academic Google Scholar J. De Bersaques, J. De Bersaques Department of Dermatology, University Hospital, De Pintelaan 185, 9000 Gent, Belgium Search for other works by this author on: Oxford Academic Google Scholar D. Platevoet, D. Platevoet Department of Dermatology, University Hospital, De Pintelaan 185, 9000 Gent, Belgium Search for other works by this author on: Oxford Academic Google Scholar A. Kint A. Kint Department of Dermatology, University Hospital, De Pintelaan 185, 9000 Gent, Belgium Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 124, Issue 3, 1 March 1991, Pages 303–305, https://doi.org/10.1111/j.1365-2133.1991.tb00587.x Published: 01 March 1991
Papez dreams: Mechanism and phenomenology of dreaming
Authors: E. E. Krieckhaus
Journal: Behavioral and Brain Sciences (2000)

I agree with Revonsuo that dreaming, particularly about risky scenes, has a great selective advantage. Although the paleoamygdala system generally facilitates stress and alarm, the system which inhibits stress and alarm, initiates bold actions, and mediates learning in risky scenes is the arche, hippocampal system (Papez circuit). Because all thalamic nuclei are inhibited during sleep except arche, Papez probably also dreams in risky scenes. [Revonsuo]
Turning the tide on conflicts of interest
Authors: F. Godlee
Journal: BMJ (2011)

The US Food and Drug Administration says it may loosen its conflict of interest policies (doi:10.1136/bmj.d5070). A shortage of independent experts means that its current rule—no more than 13% of advisers with industry ties—is delaying the introduction of new drugs, says its commissioner.

This attack of nerves is reminiscent of the New England Journal of Medicine ’s U-turn in 2002, which reversed an earlier ban on commissioning editorials and reviews from authors with ties to industry. The journal said it had found that some fields could not be covered ( N Engl J Med 2002;346:1901-2). Since then, like the BMJ and other major journals, it has asked authors to declare their …
A Note on the Association of Emphysema, Peptic Ulcer and Smoking
Authors: Francis C. Lowell, William Franklin, Alan L. Michelson, Irving W. Schiller
Journal: New England Journal of Medicine (1956)

THE following discussion suggests a relation between emphysema, peptic ulcer and smoking and tentatively places a heavy responsibility on the last in the pathogenesis of the first two. In the course of the past eighteen months, 25 patients with chronic obstructive pulmonary emphysema were studied. These patients were unselected and came under observation only because of the presence of advanced pulmonary disability. A review of the histories in this group revealed that all had been heavy smokers, and with the exception of 1 male patient who stated that he had smoked cigars exclusively, all had smoked cigarettes for twenty years . . .
Use of paclitaxel-eluting balloons for endotherapy of anastomotic strictures following liver transplantation
Authors: I. Kabar, V. Cicinnati, S. Beckebaum, S. Cordesmeyer, Y. Avsar, H. Reinecke, H. Schmidt
Journal: Endoscopy (2012)

Biliary anastomotic strictures after liver transplantation are a major source of morbidity and graft failure; however, repeated endoscopic therapy has shown variable long-term success rates. Thus the aim of this prospective case series was to evaluate the safety and efficacy of using paclitaxel-eluting balloons in 13 patients requiring treatment for symptomatic anastomotic strictures following liver transplantation. Sustained clinical success—defined as no need for further endoscopic intervention for at least 6 months – was achieved in 12 /13 patients (92 %). One, two, and three interventions were required in 9 (69 %), 1, and 2 patients, respectively (mean number of sessions was 1.46). Mean (± SD) bilirubin level dropped from 6.8 (± 4.1) mg/dL to 1.4 (± 0.9) mg/dL. These promising results justify carrying out a randomized comparative trial to confirm this innovative approach.
Pulmonary-Hepatic vascular Disorders (PHD)
Authors: R. Rodríguez-Roisin, M.J. Krowka, Ph. Hervé, M.B. Fallon
Journal: European Respiratory Journal (2004)

⇓“The tantalizing problem of the connective link in cirrhotic patients between oxygen unsaturation and possible arteriovenous shunting in the lungs remains unsolved, and any relation between arterial unsaturation and pulmonary vasodilation remains obscure.”



Fig. 1.— 
Working model of molecular alterations in the pulmonary microcirculation in experimental hepatopulmonary syndrome (HPS). a) In the normal microvasculature, a balance of vasoconstrictive and vasodilatory factors, including paracrine endothelin (ET)-1-mediated vasoconstriction through the ETA receptor (▪) on smooth muscle cells (SMCs) and ET-1-mediated vasodilatation mediated through the ETB receptor (□) linked to endothelial nitric oxide synthase (eNOS) in endothelial cells (ECs), maintain tone. b) During the development of HPS, a number of alterations, both directly and indirectly related to hepatic injury and portal hypertension, result in the production or release of mediators into the venous circulation, where they influence the pulmonary microcirculation. Increased expression of pulmonary endothelial ETB receptors and increased hepatic production and release of ET-1 contribute to an increase in eNOS expression and enhanced nitric oxide (NO) production in the microvascular endothelium during the initiation of HPS. Tumour necrosis factor (TNF)-α-mediated accumulation of intravascular macrophage-like cells also occurs after chronic common bile duct ligation. Haem oxygenase (HO)-1 and inducible nitric oxide synthase (iNOS) expression increase in these cells and contribute to the progression of HPS. CO: carbon monoxide.





Fig. 2.— 
Algorithm for screening and therapeutic decisions in hepatopulmonary syndrome (HPS). OLT: orthotopic liver transplantation; P a,O2: arterial oxygen tension; P A–a,O2: alveolar–arterial oxygen tension difference; CEE: contrast-enhanced echocardiography; PFT: pulmonary function test; MAA: macroaggregated albumin. #: high-resolution thoracic computed tomographic scanning is highly recommended in order to exclude chronic respiratory comorbid conditions; ¶: high risk for post-operative OLT mortality. 1 mmHg=0.133 kPa.





Fig. 3.— 
Plot demonstrating the relationship between cardiac output ( Q ') and transpulmonary pressure gradient (TPG; mean pulmonary arterial …
Hepatitis C Virus Infection Among Patients Attending a Clinic for Sexually Transmitted Diseases
Authors: Hillard S. Weinstock
Journal: JAMA (1993)

To evaluate the association between hepatitis C virus (HCV) infection and sexual behavior in a sexually active population.Cross-sectional study.Inner-city clinic for sexually transmitted diseases.The study included 1292 patients attending the clinic for care during a 1-month period and having syphilis serologic tests performed.Antibody to HCV (anti-HCV) positivity as defined by a repeatedly-reactive enzyme immunoassay and a positive neutralization enzyme immunoassay (Abbott Laboratories, Chicago, Ill).Of 1292 patients screened for anti-HCV, 99 (7.7%) were positive. Logistic regression analysis found that patients who reported intravenous drug use, were positive for antibody to hepatitis B core antigen, reported a history of a blood transfusion, were black, or reported crack cocaine use were more likely to be anti-HCV-positive. Forty-five percent of patients who were anti-HCV-positive reported intravenous drug use. Sex with an intravenous drug user and a history of gonorrhea and syphilis were associated with anti-HCV positivity in a univariate analysis, but after controlling for confounding variables, no such associations remained. While having multiple sexual partners in the previous 3 months, being homosexual or bisexual, and engaging in receptive anal intercourse were associated with being positive for antibody to hepatitis B core antigen, those behaviors were not associated with anti-HCV positivity.While these results cannot exclude a role for the sexual transmission of HCV, they do suggest that, in this sexually active population, the sexual transmission of HCV occurs infrequently and that HCV is largely associated with intravenous drug use.
Detection of herpesvirus DNA in peripheral blood mononuclear cells and skin lesions of patients with pemphigus by polymerase chain reaction
Authors: M.A. Tufano, A. Baroni, E. Buommino, E. Ruocco, M.L. Lombardi, V. Ruocco
Journal: British Journal of Dermatology (1999)

Pemphigus is an autoimmune disease where both endogenous (genetic) and exogenous (environmental) factors play a part. Viral infections, in particular herpesvirus infections, have been identified as a possible triggering factor for pemphigus. In this study, using the polymerase chain reaction, we studied peripheral blood mononuclear cells (PBMC) and skin biopsies from patients with pemphigus, and in some of these were able to demonstrate the presence of DNA sequences of herpes simplex virus 1/2 (50% in PBMC and 71% in skin biopsies), Epstein–Barr virus (15% in PBMC and 5% in skin biopsies) and human herpesvirus 6 (20% in PBMC only). However, the inability to detect herpesvirus DNA consistently in these cases suggests that viral infection may only be an occasional factor triggering the outbreak or exacerbation of the disease. The possible role of interferons and interleukins in the pathogenesis of virus‐induced pemphigus is discussed.