tbuckley/cabot-search huggingface dataset:
Targeted delivery of interferon-α to hepatitis B virus-infected cells using T-cell receptor-like antibodies
Authors: Changhua Ji, Konduru S.R. Sastry, Georg Tiefenthaler, Jennifer Cano, Tenny Tang, Zi Zong Ho, Denise Teoh, Sandhya Bohini, Antony Chen, Surya Sankuratri, Paul A. Macary, Patrick Kennedy, Han Ma, Stefan Ries, Klaus Klumpp, Erhard Kopetzki, Antonio Bertoletti
Journal: Hepatology (2012)

During antiviral therapy, specific delivery of interferon-α (IFNα) to infected cells may increase its antiviral efficacy, trigger a localized immune reaction, and reduce the side effects caused by systemic administration. Two T-cell receptor-like antibodies (TCR-L) able to selectively bind hepatitis B virus (HBV)-infected hepatocytes of chronic hepatitis B patients and recognize core (HBc18-27) and surface (HBs183-91) HBV epitopes associated with different human leukocyte antigen (HLA)-A*02 alleles (A*02:01, A*02:02, A*02:07, A*02:11) were generated. Each antibody was genetically linked to two IFNα molecules to produce TCR-L/IFNα fusion proteins. We demonstrate that the fusion proteins triggered an IFNα response preferentially on the hepatocytes presenting the correct HBV-peptide HLA-complex and that the mechanism of the targeted IFNα response was dependent on the specific binding of the fusion proteins to the HLA/HBV peptide complexes through the TCR-like variable regions of the antibodies.TCR-L antibodies can be used to target cytokines to HBV-infected hepatocytes in vitro. Fusion of IFNα to TCR-L decreased the intrinsic biological activity of IFNα but preserved the overall specificity of the protein for the cognate HBV peptide/HLA complexes. This induction of an effective IFNα response selectively in HBV-infected cells might have a therapeutic advantage in comparison to the currently used native or pegylated IFNα.
Intraductal papillary mucinous neoplasms (IPMNs): is it time to (sometimes) spare the knife?
Authors: C. Bassi, S. Crippa, R. Salvia
Journal: Gut (2008)

A study by Tanno et al 1 published in this issue of Gut (see page 10.1136/gut.2007.129684) shows that a branch-duct intraductal papillary mucinous neoplasms of the pancreas (BD-IPMNs) without mural nodules can be safely followed with non-operative management, confirming the results of a prospective study carried out at our institution and recently published in this journal.2

IPMNs were first described 25 years ago by Ohashi and colleagues with the name “mucin secreting cancer of the pancreas”.3 During the 1980s and early 1990s many case reports and small series of IPMNs were published but at that time IPMNs were frequently confused with other pancreatic tumours, in particular with mucinous cystic neoplasms (MCNs) of the pancreas.4 5 It was only in 1996 that the World Health Organization made a clear distinction between IPMNs and MCNs, the latter being characterised by the presence of the unique ovarian stroma with no involvement of the ductal system of the pancreatic gland.6 Mucin-producing neoplasms of the pancreas, including both IPMNs and MCNs, were considered as lesions with potential or actual malignancy, and therefore surgery was recommended for all mucinous tumours.4 5

IPMNs can affect the ductal system of the pancreas with two distinct forms: neoplasms that arise from the main duct with or without a synchronous involvement of the branch ducts (MD-IPMNs) or IPMNs involving only the secondary branches (BD-IPMNs).

The incidence of IPMNs has increased dramatically over the past 10 years and, nowadays, they represent the second indication for pancreatic resection at our institution, after ductal adenocarcinoma. This is basically related to the widespread use of cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) that led to “incidental” diagnosis of cystic neoplasms of the pancreas (including IPMNs) in a large number of asymptomatic patients. …
Management of Drug Therapy in the Elderly
Authors: S C Montamat, B J Cusack, R E Vestal
Journal: New England Journal of Medicine (1989)

DRUG therapy in the elderly is complicated by many factors unique to this age group. Because it requires careful individualization, such therapy should be based on the principles of pharmacokinetics. Multiple disease processes, environmental influences, and genetic variation often combine with the physiologic effects of aging to affect the disposition of drugs in this heterogeneous population (Table 1). It is therefore difficult to generalize about the effects of age alone. Unfortunately, there has been relatively little investigation of the effects of age at the sites of drug action. In addition, little information is available about drug disposition and response in . . .
The GENNID Study: A resource for mapping the genes that cause NIDDM
Authors: Leslie J Raffel, David C Robbins, Jill M Norris, Eric Boerwinkle, Ralph A DeFronzo, Steven C Elbein, Wilfred Fujimoto, Craig L Hanis, Steven E Kahn, M Alan Permutt, Ken C Chiu, Jaime Cruz, David A Ehrmann, R Paul Robertson, Jerome I Rotter, John Buse
Journal: Diabetes Care (1996)

OBJECTIVE To develop a resource, consisting of comprehensive data and lymphoblastoid cell lines, of well-characterized NIDDM families that will be available to the scientific community for genetic studies of NIDDM. RESEARCH DESIGN AND METHODS Non-Hispanic white, Hispanic, African-American, and Japanese-American multiplex NIDDM families, with a minimum of one affected sib-pair, are being collected by the eight Harold Rifkin Family Acquisition Centers. Detailed family and medical histories are obtained from all participants. Family members with diabetes have fasting blood samples drawn, while nondiabetic family members have an oral glucose tolerance test and, when possible, insulin sensitivity and insulin secretion measurements by frequently sampled intravenous glucose tolerance testing or euglycemic insulin clamp. Lymphoblastoid cell lines are established for all participants. RESULTS Over 1,400 individuals from ∼220 families have been studied since the start of the GENNID (Genetics of NIDDM) program in July 1993. The goal is that by July 1997, data from 300 non-Hispanic white families, &amp;gt; 100 Hispanic families, &amp;gt; 100 African-American families, and 15 Japanese-American families will have been collected. CONCLUSIONS The identification of the genes responsible for NIDDM may now be achievable, but only if sound phenotypic data are linked to genetic material from a large number of well-described multiplex families. The GENNID project of the American Diabetes Association is creating a comprehensive resource that will expedite the identification of the genetic basis of NIDDM.
Abstract B23: Cysteine (C)-X-C receptor 4 induces oxidative stress through NADPH oxidase-2 in prostate cancer cells
Authors: Kia J. Jones, Mahandranauth A. Chetram, Danaya A. Bethea, Cimona V. Hinton
Journal: Cancer Research (2013)

Abstract Reactive oxygen species (ROS), and the coupled oxidative stress, have long been implicated in the onset and progression of many cancers, including prostate cancer (PCa). One of the mechanisms by which ROS contributes to cancer is by acting as a second messenger, relaying signals from the cell surface to important signaling proteins, thereby regulating a variety of cellular processes. We have demonstrated that ROS increased the expression and activity of the chemokine (CXC) receptor, type 4 (CXCR4), which resulted in proliferation, invasion and trans-endothelial migration of PCa cells. Similarly, a study in human hepatoma cells revealed that CXCR4, and its ligand, stromal cell derived factor 1 alpha (SDF-1α), promoted ROS accumulation; however, the source (s) of ROS following growth factor stimulation have not been investigated. Identifying the sources of ROS that leads to oxidative stress in the tumor microenvironment remain areas of intense research. A recent study demonstrated that the increased ROS generation observed in PCa cell lines of varying aggressiveness was largely contributed by the NADPH oxidase family of enzymes. Herein, we observed that SDF-1α promoted ROS accumulation in C4-2 human PCa cells. We also established that NOX, an extramitochondrial ROS-generating system, was the primary source of ROS instead of the mitochondria. Moreover, expression of the isoform, NOX2, was preferentially regulated by CXCR4 at transcriptional and post-transcriptional levels. Finally, NOX2 expression correlated with PCa aggressiveness in microarray datasets. Therefore, we hypothesize that the SDF-1α /CXCR4 signaling axis mediates ROS production in PCa through NADPH-oxidases, resulting in oxidative stress that encourages tumor progression. Results generated from this study will further elucidate the mechanism (s) by which growth factor signaling promotes oxidative stress to enhance tumor development. Understanding the relationship between known cancer promoting elements, such as CXCR4, ROS and NOX, will facilitate the development of more comprehensive therapeutics to enhance current clinical strategies to combat cancer metastasis. Citation Format: Kia J. Jones, Mahandranauth A. Chetram, Danaya A. Bethea, Cimona V. Hinton. Cysteine (C)-X-C receptor 4 induces oxidative stress through NADPH oxidase-2 in prostate cancer cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B23.
Abstract 5519: <i>In vivo</i> fluorescence lifetime imaging differentiates the bound versus unbound status of a cell surface receptor targeted ligand.
Authors: Yoli JeuneSmith, Allison S. Cohen, Narges K. Tafreshi, Josef Vagner, Robert Gillies, David Morse
Journal: Cancer Research (2013)

Abstract In vivo fluorescence lifetime imaging allows for the isolation of probe-specific fluorescence lifetime from surrounding tissue auto-fluorescence. Fluorescence lifetime is not affected by agent concentration or depth, or image acquisition parameters. However, fluorescence lifetime can be affected by the in vivo tissue microenvironment, e.g. pH or hypoxia. In this work, fluorescence lifetime is used to characterize the presence and fate of a high-affinity peptidyl delta opioid receptor (δOR) ligand conjugated to the near-infrared fluorescent IRDye800CW (Li-Cor). HCT116 colorectal cancer cells engineered to over-express the δOR and parental non-expressing HCT116 cells were bilaterally xenografted subcutaneously into the flanks of athymic nude mice. At a series of time-points following tail vein injection of the ligand, in vivo fluorescence images images were acquired using the Optix MX3 scanner (Advanced Research Technologies). For 24 h, the ligand fluoresence lifetime was significantly different (p&amp;lt;0.05) in the δOR positive tumors relative to the negative tumors. At 48 hours, the fluorescence lifetime in the negative tumor decreased and was no longer different. We hypothesize that the early difference in fluorescence lifetime is attributed to the bound state of the ligand on receptor positive tumors relative to the unbound state in negative tumors. Over time, unbound ligand clears from the negative tumor leaving only a low concentration of ligand retained by non-specific interactions. In vitro studies demonstrated that the fluoresecence lifetime of this ligand is not altered within the biological pH range. However, the tumor microenvironment is complex and multiple factors may be influencing the observed differences. Future plans include studies of 3D cell cultures using varied microenvironmental conditions and studies on δOR endogenous cell lines. Citation Format: Yoli JeuneSmith, Allison S. Cohen, Narges K. Tafreshi, Josef Vagner, Robert Gillies, David Morse. In vivo fluorescence lifetime imaging differentiates the bound versus unbound status of a cell surface receptor targeted ligand. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5519. doi:10.1158/1538-7445.AM2013-5519
Diagnosing Lyme Disease
Authors: James R. Johnson
Journal: Annals of Internal Medicine (1992)

Letters1 April 1992Diagnosing Lyme DiseaseJames R. Johnson, MDJames R. Johnson, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-116-7-603_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editors:Uncritical clinical application of the T-cell proliferative assay described by Dressier and colleagues (1) may further confuse the evaluation of patients for Lyme disease. The investigators proposed that the test may be helpful in evaluating patients who have clinically apparent late-stage Lyme disease and whose humoral immune response has waned or has been aborted by early (subcurative) antibiotic therapy (1). Such circumstances are rarely encountered. Furthermore, the need for a confirmatory diagnostic test is arguable; few physicians would withhold antimicrobial therapy for Lyme disease on the basis of seronegativity when the patient's history and physical findings are...References1. Dressler F, Yoshinari N, and Steere A. The T-cell proliferative assay in the diagnosis of Lyme disease. Ann Intern Med. 1991;115:533-9. LinkGoogle Scholar2. Lettau L. From the Centers for Fatigue Control (CFC) Weekly Report. Ann Intern Med. 1991; 114:602. LinkGoogle Scholar1. Dattwyler R, Volkman D, Luft B, Halperin J, Thomas J, and Golightly M. Seronegative Lyme disease: dissociation of the specific T- and B-lymphocyte responses to Borrelia burgdorferi. N Engl J Med. 1988;319:1441-6. CrossrefMedlineGoogle Scholar2. Tosiello L, LeHau L, Madhaven T, Berman D, and Wenglin B. Lime versus Lyme disease [letters]. Ann Intern Med. 1991;115:157-8. LinkGoogle Scholar3. Gold D, Bowden R, and Sixbey J. Chronic fatigue: a prospective clinical and virologic study. JAMA. 1990;264:48-53. CrossrefMedlineGoogle Scholar4. Imboden J, Canter A, Cluff L, and Trever R. Brucellosis. III. Psychological aspects of delayed convalescence. Arch Intern Med. 1959;103:406-14. CrossrefGoogle Scholar5. Steere A. Lyme disease. N Engl J Med. 1989;321:586-96. CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: James R. Johnson, MD PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1992Volume 116, Issue 7Page: 603-603KeywordsAntibioticsAntimicrobialsHumoral immune responseLyme disease ePublished: 1 December 2008 Issue Published: 1 April 1992 PDF downloadLoading ...
Effect of population mixing and socioeconomic status in England and Wales, 1979-85, on lymphoblastic leukaemia in children
Authors: C A Stiller, P J Boyle
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objectives</b>: To examine the effects of migration, diversity of migrant origins, commuting, and socioeconomic status on the incidence of acute lymphoblastic leukaemia in childhood. <b>Design</b>: Poisson regression analysis of incidence rates in relation to the variables of interest. <b>Setting</b>: The 403 county districts of England and Wales during 1979–85. <b>Subjects</b>: Children aged under 15 years. <b>Results</b>: There were significant trends in the incidence of lymphoblastic leukaemia at ages 0–4 and 5–9 years with the proportion of children in a district who had recently entered the district. While there was no consistent relation between the proportion of recent incomers in the total population of a district and its incidence rate, the combination of higher migration with greater diversity of origins or distance moved was associated with higher incidence in both age groups. Incidence increased significantly at age 0–4 with the level of employment in a district and at age 5–9 with the proportion of households with access to a car. No significant trends were found with commuting. <b>Conclusions</b>: The results for level of child migration and diversity of total migration provide evidence of an effect of population mixing on the incidence of childhood leukaemia which is not restricted to areas experiencing the most extreme levels of mixing. <h3>Key messages</h3> Population mixing even at relatively low levels may be important in the aetiology of childhood leukaemia The results provide further epidemiological evi- dence that childhood leukaemia might be a rare response to infection Previous studies finding increased incidence in more affluent areas may have been indirectly observing a population mixing effect
DR. B. WILLDER'S CATALOGUE OF VOGUE WORDS
Authors: Robert L. Dean
Journal: JAMA (1966)

Here at last is our 1966 Catalogue—truly the biggest and best Spring collection of vogue words for scientists that Solecisms, Unlimited, has ever presented. Order now while these words are still in fashion! Have a full supply on hand for your next staff meeting, or next scientific report. Thousands of Satisfied Users of our Pompous Prose are to be found everywhere—in every hospital, office, laboratory, university, pharmaceutical company, and medical school in the land. To put together this chic collection of Vogue Words, our buyers have searched the country high and low—in the memos of government planners, in the papers of social scientists, in the speeches of politicians. Now, at last, items from the collection are available to all scientists; special discounts by the dozen and the gross. (An abbreviated edition of this catalogue first appeared in the SK&amp;F PSYCHIATRIC REPORTER, May-June, 1965.) <h3>Bizarre—</h3> at its best when misapplied to
Na+/H+ exchange in human lymphocytes and platelets in chronic and subacute metabolic acidosis.
Authors: H P Reusch, R Reusch, D Rosskopf, W Siffert, J F Mann, F C Luft
Journal: Journal of Clinical Investigation (1993)

The effect of acid-base disturbances on sodium/proton (Na+/H+) exchange has been examined in animal models; however, few data are available from human studies. To test the effect of metabolic acidosis on Na+/H+ exchange in man, as well as to examine the relationship between Na+/H+ exchange and cytosolic calcium ([Ca2+]i), we measured both variables in patients with decreased renal function with mild metabolic acidosis (pH 7.34 +/- 0.06), in normal control subjects (pH 7.41 +/- 0.02), and in subjects before (pH 7.40 +/- 0.01), and after (pH 7.26 +/- 0.04) ammonium chloride (NH4Cl) 15 g for 5 d. Lymphocytes and platelets were loaded with the cytosolic pH (pHi) indicator 2'-7'-bis(carboxyethyl)-5,6-carboxyfluorescein and acidified to pH approximately 6.6 with propionic acid. To quantitate Na+/H+ exchange, dpHi/dt was determined at 1 min. [Ca2+]i was measured with fura-2. Na+/H+ exchange was significantly increased only in lymphocytes of patients with renal insufficiency. Neither intracellular pH (pHi) nor [Ca2+]i was different from controls. NH4Cl resulted in a significant increase in Na+/H+ exchange in lymphocytes, but not in platelets of normal subjects. Values of pHi and [Ca2+]i in either cell type remained unaffected. Since metabolic acidosis influenced Na+/H+ only in lymphocytes, but not in platelets, it is possible that protein synthesis may be involved in increasing Na+/H+ exchange.
Multiplex PCR of sonication fluid accurately differentiates between prosthetic joint infection and aseptic failure
Authors: María Eugenia Portillo, Margarita Salvadó, Lluisa Sorli, Albert Alier, Santos Martínez, Andrej Trampuz, Julià Gómez, Lluis Puig, Juan Pablo Horcajada
Journal: Journal of Infection (2012)
Reading for Pleasure: Ali Baba's cave
Authors: L J Temple
Journal: BMJ (1981)

The junior library, to which the under 14s were limited, did not permit borrowers to inspect the books.Titles were chosen from the catalogue, asked for across the counter, and a tab from the book inserted into the borrower's ticket.Filing did not take place until the library closed.This had the disadvantage that the book could not be changed until the next day, a fact of little consequence in term time, but disastrous in the holidays.
Biopsy Needle Transplanting Tumor?
Authors: NATHAN S. SERIFF
Journal: Annals of Internal Medicine (1970)

Letters and Comments1 January 1970Biopsy Needle Transplanting Tumor?NATHAN S. SERIFF, M.D.NATHAN S. SERIFF, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-1-145 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Wolinsky and Lischner, in their interesting article "Needle Track Implantation of Tumor after Percutaneous Lung Biopsy," in the August 1969 issue of the ANNALS OF INTERNAL MEDICINE, suggest strongly that the Franklin-Silverman needle biopsy of the right-upper-lobe carcinoma in their patient resulted in implantation of the tumor in the soft tissues of the anterior chest wall.It is possible, however, that there is another explanation for the mass that developed in the right anterior chest wall several months after the biopsy. In view of the fact that the lung cancer was in the anterior segment of the...Reference1. DAHLGRENNORDENSTROM SB: Transthoracic Needle Biopsy, Chicago, Year Book Medical Publishers, Inc., 1966. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Division of Pulmonary Medicine Triboro Hospital The Long Island Jewish Hospital Queens Hospital Center Affiliatio 82-68 164 St. Jamaica, N.Y. 11432 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 January 1970Volume 72, Issue 1Page: 145-145KeywordsBiopsyLung and intrathoracic tumorsSoft tissuesThorax Issue Published: 1 January 1970 PDF DownloadLoading ...
AUTO-INFECTION AND PATHOGENIC PHYSIOLOGY.
Authors: C. B. NEWTON
Journal: JAMA (1898)

The increasing knowledge of pathologic anatomy and pathogenic physiology tends to evolution in therapeutics affecting our remedial agents. We discover that they have more or less definite value; they have their rise and fall. The drug extolled today by high authority we find does not come up to the manifesto of the manufacturing chemist and may be obsolete tomorrow. When antifebrin was first introduced, a child was brought from New York City for treatment. Their physician had prescribed this drug in 2-grain doses, to be given every two hours if there should be a rise in temperature. After they had given it for a couple of days, the nurse noticed cyanosis and coldness of the extremities, with failing pulse. This fact was a valuable one to us. It is now found to have its effect as an antipyretic by depressing the heart, it has a directly paralyzing action upon the