tbuckley/cabot-search huggingface dataset:
Interaction of woodchuck hepatitis virus surface antigen with hepatocyte plasma membrane in woodchuck chronic hepatitis
Authors: Tomasz I. Michalak, Norma D. Churchill
Journal: Hepatology (1988)

The extent of association between woodchuck hepatitis virus surface antigen and host hepatocyte plasma membrane in chronic hepatitis was studied. Purified membranes containing the antigen were treated with various agents which perturb plasma membrane constituents to elute woodchuck hepatitis virus surface antigen. The products from disrupted membranes were analyzed by sedimentation in sucrose gradients and tested to identify the antigen reactivity. The results indicated that membrane-bound wood-cauck hepatitis virus surface antigen was partially released by 4 M potassium chloride, potassium thiocyanate and guanidine, 6 M urea or 0.1 N sodium hydroxide (pH 13.5), but not in the presence of low concentrations of these reagents or by 10% 2-mercaptoethanol and 1% sodium dodecyl sulfate. No more than 15% of the total membrane-associated woodchuck hepatitis virus surface antigen was eluted by 0.1 N NaOH, which was found to be the most effective eluent among tested agents at the antigen removal. The remaining woodchuck hepatitis virus surface antigen was resistant to further extraction with sodium hydroxide, as expected for an integral membrane protein. Treatment of the infected membranes with 1% Triton X-100 or 50 m M deoxy-cholic acid, that solubilize the membrane lipid bilayer releasing most of the integral membrane proteins, resulted in the sedimentation of almost all detectable woodchuck hepatitis virus surface antigen reactivity with the detergent-insoluble membrane residues, suggesting a firm interaction of the antigen with the plasma membrane matrix. Partition of the membrane peripheral and integral proteins in 1% Triton X-114 into hy-drophilic and hydrophobic protein fractions, respectively, provided additional evidence that most of the detectable woodchuck hepatitis virus surface antigen reactivity within the infected membranes was associated with their integral proteins. The results demonstrate that woodchuck hepatitis virus surface antigen found in hepatocyte plasma membrane behaves as a peripheral and an integral membrane protein. It was shown that most of the woodchuck hepatitis virus surface antigen behaving as an integral membrane protein interacts extremely extensively with the membrane. This unexpectedly strong membrane binding of woodchuck hepatitis virus surface antigen may be irreversible in naturally occurring conditions and could be eliminated only by lysis of infected hepatocyte membranes. Viral envelope material firmly associated with hepatocyte plasma membrane may constitute an important element of a complex mechanism leading to persistence of the virus infection that could also be responsible for preservation of hepatocytes with integrated viral genome.
Biological Aberrations Associated with Malignant Diseases.
Authors: G. Lennard Gold
Journal: Annals of Internal Medicine (1965)

s1 November 1965Biological Aberrations Associated with Malignant Diseases.G. Lennard Gold, M.D., Bruce I. Schnider, M.D., F.A.C.P., John Lynch, M.D.G. Lennard Gold, M.D.Search for more papers by this author, Bruce I. Schnider, M.D., F.A.C.P.Search for more papers by this author, John Lynch, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-916_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn recent years, a variety of syndromes occurring in the presence of so-called nonfunctioning tumors have been reported. Benign tumors as well as malignant growths have been indicted as the cause of disturbances in physiology in the patient with a tumor. These peculiarities of metabolic function are significant for in some situations they are curable while in others they may herald the appearance of a tumorous growth before the tumor itself is clinically apparent. Hopefully by unraveling the biological mechanisms governing their occurrence, a better understanding of disease processes may be obtained.We have categorized the 42 unusual syndromes that... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Washington, D. C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 916-917KeywordsBenign tumors Issue Published: 1 November 1965 PDF downloadLoading ...
Hepatic SPECT Imaging in the Detection and Clinical Assessment of Hepatocellular Disease
Authors: RONALD L VAN HEERTUM, ANTHONY P. YUDD, JACQUELINE C. BRUNETTI, MARK R. PENNINGTON, NICHOLAS M. GUALTIERI
Journal: Clinical Nuclear Medicine (1992)

A total of 95 patients, including 45 people with no evidence of liver disease and 50 documented hepatocellular disease patients, were studied to assess the value of planar and SPECT scintigraphy in the evaluation of hepatocellular disease. The accuracy and concordance between techniques was assessed using two criteria. Criterion 1, heterogeneity of the tracer in liver, yielded a concordance of 64%, whereas with criterion 2, liver and spleen tracer pattern, concordance was 78%. SPECT was significantly more accurate than planar imaging (P < 0.01), using both criteria. The clinical severity of the hepatocellular disease was further assessed in 72 of the patients and correlated with a liver scan severity rating scale. The SPECT technique showed a good correlation (r = 0.89) with the composite clinical severity score; however, no significant relationship with planar imaging was noted. The results of this study suggest that liver SPECT is a reliable technique for the assessment of hepatocellular disease.
199 THE EFFECTS OF DISEASE STAGE AND ACUTE-ON-CHRONIC LIVER FAILURE ON THE PROFILE OF PLASMA DIMETHYLARGININES IN CIRRHOSIS
Authors: S.J. Thomson, M.L. Cowan, S. Musa, R.N. Dalton, C. Turner, D.M. Forton, S.J. Clark, T.M. Rahman
Journal: Journal of Hepatology (2010)
Comparison of Meeting Abstracts and Subsequent Articles
Authors: Chi-Tai Fang, Loreen Y. L. Huang
Journal: JAMA (2006)

To the Editor: In their study evaluating the degree of consistency between meeting abstract and subsequent fulllength journal article, Dr Toma and colleagues 1 found discrepancies between the efficacy estimate for the primary outcome in 60 (41%) of the 148 randomized controlled trials.This highlights the need for scrutiny of the quality of information from randomized controlled trials.There is another often neglected issue: the percentage of patients meeting inclusion criteria who actually entered randomization. 2 This important index tells a lot about the design and conduct of randomized controlled trials.While it is rare for all eligible patients to be willing to participate in a randomized trial, if the percentage is too low it raises questions about why so many patients would decline to join.Did they or their physicians feel the risk-benefit ratio of joining this trial was unfavorable?Were only those who were most likely to benefit from the new treatment invited to participate?If so, what were the real inclusion criteria?Perhaps the lack of logistic support was the true reason for selective enrollment.Both the number of eligible patients and the number of patients who actually entered randomization are part of the required information for the CONSORT E-Flowchart. 3Unfortunately, many authors do not report this information in their articles; it is not clear why some authors provide this information and other do not.Mandatory reporting of the percentage of eligible patients who actually entered randomization of phase 3 and later-stage clinical trials would create an incentive for better design of clinical trial protocols, better specification of inclusion criteria, and better logistic operations.
Patient-reported outcome measures in skin cancer
Authors: N. Black
Journal: British Journal of Dermatology (2013)

Journal Article Patient‐reported outcome measures in skin cancer Get access N. Black N. Black Department of Health Services Research and Policy London School of Hygiene and Tropical Medicine 15–17 Tavistock Place London WC1H 9SH U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 168, Issue 6, 1 June 2013, Page 1151, https://doi.org/10.1111/bjd.12406 Published: 01 June 2013
Motor-cycle Accidents
Authors: E. R. Nye
Journal: BMJ (1959)

Klüver-Bucy syndrome is a rare neurobehavioral disorder caused by a bilateral temporal lobe lesion affecting the hippocampus and amygdala; clinically characterised by hyperorality, hypermetamorphosis, placidity, altered sexual behaviour, eating, disorders and visual impairment, agnosia and amnesia. However, the complete syndrome is rarely seen, and diagnosis does not require all the symptoms to be manifested simultaneously. We describe a patient who developed a complete Klüver-Bucy syndrome secondary to bilateral temporal involvement due to herpetic encephalitis.
Management of pyoderma gangrenosum
Authors: Alexandra Teagle, Rachel Hargest
Journal: Journal of the Royal Society of Medicine (2014)

Pyoderma gangrenosum (PG) is an uncommon ulcerative skin disease often associated with underlying systemic diseases. Its pathogenesis is unknown, although immune pathways have been implicated. Targeted therapy is therefore lacking and currently treatment is largely empirical and consists of corticosteroids and ciclosporin first line. This paper reviews the current and emerging knowledge about PG. PG occurs with an incidence of 3-10 per million per year. The ulcers are exquisitely painful and characteristically have a necrotic centre with irregular overhanging bluish borders. Around half of cases are associated with underlying systemic disease, most commonly inflammatory bowel disease, rheumatoid arthritis and haematological malignancies; the remaining cases are idiopathic. The pathogenesis is unknown, but the most widely supported theory is immunological, and biopsies of lesions show a predominantly neutrophilic infiltrate. Several aberrant immune processes have been described, with neutrophils and their recruitment to sites of inflammation by cytokines taking an apparently important role. Topical and systemic therapies are both vital aspects of treatment, and in recent years, immune modulators have been used with increasing success, with an emerging role for anti-tumour necrosis factor alpha agents such as the monoclonal antibody infliximab. Although uncommon, PG causes significant morbidity to those it affects. Further research is needed into the disease pathogenesis, and adequate targeted treatment.
Atypical antipsychotic drugs
Authors: P. Mackin, S. H. L. Thomas
Journal: BMJ (2011)

#### Case scenario

A 19 year old student has a six month history of social withdrawal, and bizarre behaviour. He becomes suspicious of his fellow students and believes that his teachers are monitoring his activity on Facebook. He is heard laughing and shouting when he is alone. Paranoid psychosis is diagnosed, and an atypical antipsychotic drug is prescribed alongside other psychosocial interventions (a combination recommended by current guidelines from the National Institute for Health and Clinical Excellence (NICE)1

The “typical” (first generation) antipsychotic drugs (such as haloperidol, chlorpromazine, and trifluoperazine) have been used to treat schizophrenia since the 1950s. The “atypical” (second generation) antipsychotics (table 1⇓) were introduced into routine practice from the 1990s. Both classes are used in the acute phase of schizophrenia and related psychoses and for long term maintenance and prevention of relapse. Typical antipsychotic drugs have a range of adverse effects, notably extrapyramidal features such as dystonia, parkinsonism, akathisia, and tardive dyskinesia. Although atypical antipsychotics are less likely to cause extrapyramidal symptoms, they may also have important adverse effects, including metabolic effects.3 Some atypical antipsychotics are also licensed to treat mood disorders, and table 1⇓ summarises licensed indications in the United Kingdom. However, this article considers their use for the treatment of non-affective psychosis only.

View this table:

Table 1 
 Current licensed (UK) atypical antipsychotics, with their licensed indications and available formulations2



Antipsychotics are a pharmacologically heterogeneous group of compounds, but all act as D2 dopamine receptor antagonists, an action linked to their antipsychotic effect.4 While the term atypical originally referred to antipsychotic drugs that did not cause catalepsy in animal models, recent academic and marketing literature uses this term to refer to both clinical properties (reduced incidence of extrapyramidal effects) and chemical properties (receptor profile).5 6 5-HT2A antagonism and/or 5-HT1A agonism may be …
THE ACTION AND USES OF THE ANTIHISTAMINE DRUGS AS APPLIED TO DERMATOLOGY*
Authors: HENRY H. DALE
Journal: British Journal of Dermatology (1950)

Journal Article THE ACTION AND USES OF THE ANTIHISTAMINE DRUGS AS APPLIED TO DERMATOLOGY Get access HENRY H. DALE, O.M., G.B.E., F.R.C.P., F.R.S. Sir HENRY H. DALE, O.M., G.B.E., F.R.C.P., F.R.S. Sir Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 62, Issue 4, 1 April 1950, Pages 151–158, https://doi.org/10.1111/j.1365-2133.1950.tb10980.x Published: 01 April 1950
Hearing and Vision Care for Older Adults
Authors: Heather E. Whitson, Frank R. Lin
Journal: JAMA (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract B63: Cancer cell invasion determined by cell density-dependent, cytokine-mediated crosstalk
Authors: Ghada M. Sharif, Marcel O. Schmidt, Zhang-Zhi Hu, Eric Glasgow, Anna T. Riegel, Anton Wellstein
Journal: Cancer Research (2013)

Abstract Metastatic spread of cancer cells from their primary site requires invasion into the vasculature, evasion at the distant organ site and colonization of the distant organ. Here we studied mechanisms of attachment and invasion into endothelial monolayers by cancer cells to identify driver molecules and signaling pathways that are crucial for the invasive and metastatic phenotype. In vitro studies were complemented by studies in zebrafish embryos and mouse models of cancer cell invasion and metastasis. In one approach we compared gene expression profiles across isogenic cell lines with distinct invasive behavior to identify candidate drivers and pathways. These were then subjected to functional validation. This comparison of gene expression profiles of isogenic cancer cell lines showed an upregulation of immune response cytokines associated with an endothelial invasive phenotype in human breast cancer cells. The role of the respective cytokine pathways was validated by blocking the respective receptors in in vitro assays and in a zebrafish metastasis model. Citation Format: Ghada M. Sharif, Marcel O. Schmidt, Zhang-Zhi Hu, Eric Glasgow, Anna T. Riegel, Anton Wellstein. Cancer cell invasion determined by cell density-dependent, cytokine-mediated crosstalk. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B63.
Five Years Clinical Experience with 5-Fluorouracil
Authors: Fred J. Ansfield
Journal: JAMA (1962)

During the past 5 years, 5-fluorouracil (5-FU) was used to treat 1,091 patients with from 1 to 54 courses. An attempt was made to treat each patient to slight toxicity with each course of therapy given at monthly intervals except poor-risk patients who either were not treated or given a poor-risk schedule. Of 428 patients with measurable lesions treated with 5-FU, 91 met all our criteria of improvement for an average duration of 9 months before reactivation of the disease occurred. The lesions found most responsive to the drug were cancer of the breast, colon or rectum, stomach, cervix, ovary, and malignant hepatoma. Squamous-cell carcinoma of the head and neck, carcinoma of the lung, hypernephroma, and malignant melanoma were unresponsive.
THE METHODS OF DRAINAGE NOW PREVAILING IN SOME OF OUR EASTERN SEABOARD MUNICIPALITIES, TENDING TO THE PRODUCTION AND DISSEMINATION OF DISEASE.
Authors: AUGUSTUS P. CLARKE
Journal: JAMA (1896)

Crudely constructed latrines and cesspools, without connections with regularly laid drains, were the devices which often obtained among the early inhabitants of the country; they were places for receiving the waste water and the dejecta of occupants of houses and other buildings, and were for the most part recommended merely for the convenience they afforded. The method which these contrivances furnished for disposing of refuse liquids and excrementitious elements worked no serious manifest injury unless some of the more deleterious products had gained, by percolating through the surrounding soil, admission into a well or other source of water to be used for domestic purposes. Among the more dangerous products of this class have been those derived from the albuminoids and the nitrates, and from carriers of some of the forms of bacteria that were capable of giving rise to diseases that have been regarded as of a zymotic character. The
1111. TAT-Streptavidin: A Novel Drug Delivery Vector for the Intracellular Uptake of Macromolecular Cargo
Authors: Brian Albarran, Richard To, Patrick Stayton
Journal: Molecular Therapy (2005)

Top of pageAbstract
Summary |[ndash]| The TAT protein transduction domain has been used extensively for directing the intracellular delivery of proteins to which it is conjugated, complexed, or fused 1,2,3,4. Streptavidin represents a potentially useful TAT-fusion protein because it could be used to deliver a wide array of biotinylated cargo. Here we have characterized a TAT-Streptavidin (TAT-SA) fusion protein, which retains the ability to bind biotinylated cargo while directing their efficient cellular uptake. We demonstrate that TAT-SA can be used to direct intracellular delivery of various bioactive cargo to intracellular compartments and that biotinylated PPAA can direct cytoplasmic delivery where desired.

Results |[ndash]| FACS analysis of TAT-SA-treated Jurkat cells confirmed nearly 100% uptake as compared with WT-SA-treated cells after 3 h. Trypsinization and treatment with an impermeable fluorescence quenching antibody seperately confirmed that the majority of cell-associated fluorescence was from internalized protein and not due to an extracellular membrane-bound fraction.

Confocal microscopy of live WT-SA-treated Jurkat cells 3 h after treatment showed little to no fluorescence, consistent with low-level, non-specific uptake, while cells treated with TAT-SA displayed punctate patches of intracellular fluorescence, indicative of an endosomal entry pathway. The ability of a pH-responsive polymer poly(propylacrylic acid) (PPAA) to enhance cytoplasmic delivery of TAT-SA was investigated 5,6. Images of live Jurkat cells 4 h after incubation with TAT-SA:PPAA complexes were characterized by a diffuse cytoplasmic distribution, in contrast to the compartmentalization seen in the absence of an endosomal disrupting polymer. Subcellular fractionation was performed to quantify the uptake of TAT-SA and the effect of PPAA on the intracellular distribution within various subcellular compartments.

The ability of TAT-SA:PPAA complexes to deliver a bioactive cargo protein to the cytoplasm was investigated with the nonphosphorylatable, nondegradable superrepressor I|[kappa]|B|[alpha]| (srI|[kappa]|B|[alpha]|) mutant which has been demonstrated as a potent inhibitor of NF-|[kappa]|B activity when expressed in cells 7. Here, purifed, biotinylated srI|[kappa]|B|[alpha]| was delivered to a 57A HeLa cell line which had been genetically engineered with a Luc reporter gene downstream of NF-|[kappa]|B promoter elements 8. TAT-SA:PPAA:srI|[kappa]|B|[alpha]| complexes inhibited TNF-|[alpha]|-induced NF-|[kappa]|B activation by nearly 50% (p<0.001) in treated cells after 4 h, demonstrating the potential of the TAT-SA:PPAA complex as an effective intracellular delivery vector.

This work thus demonstrates that TAT-SA and PPAA can be used jointly as a biomolecular vector for delivering heterogeneous cargo proteins of large size in an apparent step-wise uptake and endosomal release mechanism.
Aeroallergen and food IgE sensitization and local and systemic inflammation in asthma
Authors: A. Patelis, C. Janson, M. P. Borres, L. Nordvall, K. Alving, A. Malinovschi
Journal: Allergy (2014)

Background We recently reported an independent association between IgE sensitization to food allergens and increased airway inflammation, assessed by fraction of exhaled nitric oxide (FeNO), in a population-based study (J Allergy Clin Immunol, 130, 2012, 397). Similar studies have not been performed in populations with asthma. The aim of the present study was to investigate the allergic sensitization profile in asthmatics and examine FeNO, airway responsiveness and blood eosinophilia in relation to type and degree of IgE sensitization. Method FeNO, airway responsiveness, blood eosinophil count (B-Eos) and IgE sensitization to food allergens and aeroallergens were determined in 408 subjects with asthma, aged 10–34 years. Results Asthmatics had higher prevalence of IgE sensitization against all allergens than controls (P < 0.001). Mite, pollen, furry animal, mould and food sensitizations were each associated with increased FeNO, airway responsiveness and B-Eos in asthmatics. IgE sensitization to mould, furry animals and food allergens was independently related to FeNO (all P < 0.05) after adjustment for age, sex, height, smoking history and medication. IgE sensitization to mould (P < 0.001) and furry animals (P = 0.02) was related to airway responsiveness in a similar model. Finally, IgE sensitization to mould (P = 0.001), furry animals (P < 0.001) and food allergens (P < 0.001) was independently related to B-Eos. Conclusion Independent effects of IgE sensitization to aeroallergens (furry animals and mould) and food allergens were found on both local and systemic markers of inflammation in asthma. The finding regarding food IgE sensitization is novel, and a clinical implication might be that even food sensitization must be assessed to fully understand inflammation patterns in asthma.