tbuckley/cabot-search huggingface dataset:
Adhesion-activating phorbol ester increases the mobility of leukocyte integrin LFA-1 in cultured lymphocytes.
Authors: D F Kucik, M L Dustin, J M Miller, E J Brown
Journal: Journal of Clinical Investigation (1996)

Lymphocytes activate adhesion to intracellular adhesion mlecule 1 (ICAM-1) via leukocyte function associated antigen 1 (LFA-1), their major beta 2 integrin, in response to PMA (phorbol 12-myristate 13-acetate) without an increase in the number of receptors expressed. The molecular details of the mechanism are unknown. To determine the effect of PMA activation on LFA-1 movement within the plasma membrane, we used the single particle tracking technique to measure the diffusion rate of LFA-1 molecules on EBV-transformed B cells before and after PMA activation. Diffusion of LFA-1 on unactivated cells was restricted compared to CR1 (CD35), another transmembrane protein of equivalent size. PMA caused a 10-fold increase in the diffusion rate of LFA-1 without any effect on CD35. The increased LFA-1 motion induced by PMA was random, not directed, indicating that it was due to a release of constraints rather than the application of forces. The diffusion rates of LFA-1 are consistent with cytoskeletal attachment before and free diffusion after PMA. Cytochalasin D led to an equivalent increase in mobility and, at low doses, stimulated adhesion, implying that the nonadhesive state of LFA-1 is actively maintained by the lymphocyte cytoskeleton.
Properties and structure-function relationships of veltuzumab (hA20), a humanized anti-CD20 monoclonal antibody
Authors: David M. Goldenberg, Edmund A. Rossi, Rhona Stein, Thomas M. Cardillo, Myron S. Czuczman, Francisco J. Hernandez-Ilizaliturri, Hans J. Hansen, Chien-Hsing Chang
Journal: Blood (2008)
738 Omega-3 polyunsaturated fatty acids: A pilot trial in non-alcoholic fatty liver disease
Authors: L. Spadaro, O. Magliocco, D. Spampinato, S. Piro, C. Oliveri, C. Alagona, G. Papa, A.M. Rabuazzo, F. Purrello
Journal: Journal of Hepatology (2006)
Perfluorinated Compounds, Polychlorinated Biphenyls, and Organochlorine Pesticide Contamination in Composite Food Samples from Dallas, Texas, USA
Authors: Arnold Schecter, Justin Colacino, Darrah Haffner, Keyur Patel, Matthias Opel, Olaf Päpke, Linda Birnbaum
Journal: Environmental Health Perspectives (2010)

The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357-362].In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American.Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p -dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels.Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.
Child Abuse
Authors: JOHN R. STY, ROBERT G. WELLS
Journal: Clinical Nuclear Medicine (1994)

A 2-year-old girl was physically abused. Radiographs showed several fractures in the extremities that are typical in child abuse. Computed tomography showed an acute liver hematoma. Radionuclide bone imaging showed multiple fractures and extraosseous accumulation of bone imaging radiopharmaceutical in the liver, kidneys, and soft tissues. The diagnosis of child abuse must be included in the differential diagnosis when skeletal scintigraphy shows abnormally prominent soft tissue localization in infants and young children.
The disappointment of the double helix: a master theory
Authors: Alan Ebringer
Journal: Journal of the Royal Society of Medicine (2010)

The article by James Le Fanu1 brings to attention the huge discrepancy between the unalloyed promise of great medical benefits from unravelling the human genome and the meagre practical benefits so far achieved.

The fundamental flaw in the ‘Human Genome Project’ is that it has been forgotten that genes do not exist by themselves but are embedded in a biological and terrestrial milieu called the ‘environment’. The attempt to provide monogenic explanation for common diseases is thus mistaken.

The problem can be illustrated by the case of ankylosing spondylitis (AS), where 96% of the patients possess HLA-B27 while it is present in only 8% of the general population.2 Although some 10–20% of HLA-B27 positive individuals have some features of AS (backache, muscle stiffness), the majority are symptom-free.

Molecular mimicry between the gene product and environmental bowel bacteria, such as Klebsiella, provides a simple explanation which has therapeutic implications. Antibodies to Klebsiella have been found in AS patients from 14 different countries,3 yet expensive tri-continental studies do not provide an explanation for the high frequency of HLA-B27 in this disease.

A similar situation occurs in rheumatoid arthritis (RA), where some 90% of patients possess the ‘shared epitope’ (EQRRAA) found in HLA-DR1/4 molecules while it is present in only one-third of the general population.4 Molecular mimicry between the ‘shared epitope’ and the sequence ESRRAL found in Proteus haemolysin indicates that RA is associated with a common microbe.5

An analysis using ‘Popper sequences’ clearly shows that genes linked to RA require the intervention of an environmental factor, namely an upper urinary tract infection by Proteus bacteria.6

The rationale for expensive, multicentre genome studies in common diseases would appear to require some critical discussion and revision.
Abstract 14: Drug sensitivity of vascularized tumor tissue <i>in vitro</i>
Authors: Seema M. Ehsan, Masahiro Inoue, Marian L. Waterman, Christopher C. Hughes, Steven C. George
Journal: Cancer Research (2014)

Abstract While there have been significant advances in using 3D culture systems to recapitulate physiological aspects of the tumor microenvironment, few systems are able to capture the full range of authentic, complex in vivo processes such as neovascularization and metastasis. Furthermore, these systems generally utilize established cell lines which compromise the clinical relevance. The goal of this study was to create a 3D in vitro model of patient-specific vascularized tumor tissue that could be used to evaluate the sensitivity to F-fluoruracil (5-FU). Colon cancer cells isolated directly from patient biopsies and endothelial colony forming cell-derived endothelial cells (EC) from cord blood were combined to form multicellular spheroids, and then embedded in a fibrin gel containing normal stromal cells (primary human lung fibroblasts). After 7 days in culture, these “prevascularized tumors” (PVTs) exhibited robust sprouting angiogenesis into the surrounding matrix, and also formed a distinct and contiguous vessel network within the spheroid itself. Network formation and branching of the sprouting vessels was comparable to those generated by co-culture spheroids of EC and cells from the colon cancer cell line SW620. These spheroids in particular demonstrated intravasation of single cells within the lumens of the vessel networks. This phenomenon was enhanced in low oxygen, and abrogated by silencing the transcription factor Slug. Thus, this phenomena is consistent with endothelial-mesenchymal transition. The PVTs have furthermore been used to distinguish the effects of EC on SW620 viability in response to 5-FU. Spheroids composed of EC and SW620 cells demonstrated decreased sensitivity to low dosage 5-FU treatment compared to spheroids composed of SW620 cells only, implicating potential EC-induced drug resistance. Our results demonstrate the utility of a 3D model system of the tumor microenvironment that may be used to study intravasation, microvessel formation, and sensitivity to anti-cancer drugs. Citation Format: Seema M. Ehsan, Masahiro Inoue, Marian L. Waterman, Christopher CW Hughes, Steven C. George. Drug sensitivity of vascularized tumor tissue in vitro. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 14. doi:10.1158/1538-7445.AM2014-14
Immunologic Dissonance: A Continuing Evolution in Our Understanding of the Systemic Inflammatory Response Syndrome (SIRS) and the Multiple Organ Dysfunction Syndrome (MODS)
Authors: Roger C. Bone
Journal: Annals of Internal Medicine (1996)

Our current understanding of sepsis and multiple organ dysfunction needs to be revised, as the uniformly negative results of new therapies for these disorders suggest.Previous theories for the pathogenesis of these conditions are incomplete; reasons for this include the following. First, the surrogate models that have been used to study these disorders are not analogous to the clinical situation. Second, patients who have less severe manifestations of these diseases are often overlooked. And third, patients' preexisting conditions have not been taken into account. Considerable new evidence indicates that, in addition to a massive proinflammatory reaction, a compensatory anti-inflammatory response contributes to the onset of these disorders. At a local site of injury or infection and during the initial appearance of pro- and anti-inflammatory mediators in the circulation, the beneficial effects of these mediators outweigh their harmful effects. Only when the balance between these two forces is lost do these mediators become harmful. Sequelae of an unbalanced systemic proinflammatory reaction include shock, transudation into organs, and defects in coagulation. An unbalanced systemic compensatory anti-inflammatory response can result in anergy and immunosuppression. The proinflammatory and anti-inflammatory forces may ultimately reinforce each other, creating a state of increasingly destructive immunologic dissonance.
Ozone and Pulmonary Proteolysis
Authors: ROBERT S. HOLZMAN
Journal: Annals of Internal Medicine (1970)

Letters and Comments1 July 1970Ozone and Pulmonary ProteolysisROBERT S. HOLZMAN, M.D.ROBERT S. HOLZMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-73-1-140_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In their editorial on antitrypsin deficiency Falk and Briscoe (Ann Intern Med 72:427-429, 1970) point out that intrapulmonary proteolysis might be due to either decreased inhibitor or excess enzyme. They suggest that air pollutants might injure pulmonary cells and increase the rate of enzyme release.Ozone is a major oxidant pollutant. When rabbits and mice were exposed to concentrations higher than those usually noted in the atmosphere, the amount of lysozyme which could be extracted from bronchial secretions decreased linearly with ozone concentration. The rate of release of lysozyme from pulmonary cells of exposed animals was not...Reference1. HOLZMAN R, GARDNER D, and COFFIN D: In vivo inactivation of lysozyme by ozone. J Bact 96:1562-1566, 1968 CrossrefMedlineGoogle Scholar1. STOKINGER H: Pollutant gases, in Handbook of Physiology, vol II, edited by FENN WO, RAHN H, Washington, D.C., American Physiology Society, 1965, pp. 1068-1077 Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT S. HOLZMAN, M.D.Affiliations: New York University Medical Center School of Medicine New York, N.Y. 10016 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 July 1970Volume 73, Issue 1 Page: 140-140 Keywords Air pollution Attention Cells Enzymes Lysozyme Proteolysis Rabbits ePublished: 1 December 2008 Issue Published: 1 July 1970 PDF downloadLoading ...
Painting is earliest example of portrayal of Downs syndrome
Authors: R. Dobson
Journal: BMJ (2003)

Psychiatrists have identified what is believed to be one of the earliest paintings of someone with Down's syndrome.

The 1515 Flemish painting, by an unknown artist, considerably predates John Langdon Down's first description of the condition in 1866. It shows an angel (next to Mary)—and possibly one other figure, the shepherd in the centre of the background—with the syndrome.

“If our diagnosis is correct, this implies that Down's syndrome is not a modern disease,” say the …
Joint Study of Extracranial Arterial Occlusion
Authors: Raymond B. Bauer
Journal: JAMA (1969)

Surgical or nonsurgical treatment was randomly selected for 1,225 patients with occlusive cerebrovascular disease. Statistically significant differences in cumulative survival rate at 42 months were as follows: (1) Surgical treatment appeared more beneficial for unilateral carotid artery stenosis in patients with transient attacks or a mild-to-moderate neurological deficit. (2) Nonsurgical treatment produced better results for unilateral carotid artery stenosis in patients with a moderateto-severe neurological deficit. (3) Nonsurgical treatment appeared more beneficial for combined unilateral carotid artery stenosis and contralateral carotid artery occlusion if patients had a moderate-to-severe neurological deficit. (4) Nonsurgical treatment appeared more beneficial for patients with completed strokes who had a marked and persistent neurological deficit.
New Guidelines Focus on Preventing Stroke in Women
Authors: Mike Mitka
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
1111-212 Left ventricular asynchrony predicts heart failure progression after cardiac resynchronization therapy
Authors: Maria V Pitzalis, Massimo Iavoviello, Roberta Romito, Pietro Guida, Giovanni Luzzi, Stefania Greco, Cinzia Forleo, Brian Rizzon, Elisabetta De Tommasi, Luigi Di Biase, Paolo Rizzon
Journal: Journal of the American College of Cardiology (2004)
The Presenting Manifestations of Lyme Disease and the Outcomes of Treatment
Authors: Allen C. Steere, Vijay K. Sikand
Journal: New England Journal of Medicine (2003)

To the Editor: A trial of vaccination against Lyme disease provided an opportunity for us to determine the relative frequencies of the presenting manifestations of Lyme disease and the outcomes of treatment in a large population.1 Our goal was to identify all cases of Borrelia burgdorferi infection that occurred among the 10,936 participants in 10 states where the infection is endemic during the 20-month study period. Of the 1917 participants who were evaluated for Lyme disease, 269 met the prospectively defined criteria for definite, possible, or asymptomatic infection.1 After completion of the study, post hoc analyses were performed for patients . . .
Thermic effect of infused glucose and insulin in man. Decreased response with increased insulin resistance in obesity and noninsulin-dependent diabetes mellitus.
Authors: E Ravussin, C Bogardus, R S Schwartz, D C Robbins, R R Wolfe, E S Horton, E Danforth, E A Sims
Journal: Journal of Clinical Investigation (1983)

The thermic effect of infused glucose and insulin was measured by combining the hyperinsulinemic euglycemic clamp technique with indirect calorimetry, in 10 normal weight volunteers (group I), 7 obese subjects with normal glucose tolerance (group II), and 13 obese subjects with abnormal glucose tolerance or noninsulin-dependent diabetes mellitus before (group IIIa) and after weight loss of 10.8 +/- 0.4 kg (group IIIb). During hyperinsulinemia (760-1,100 pmol/liter), total glucose disposal from combined endogenous production and glucose infusion was 545 +/- 49, 441 +/- 70, 233 +/- 35, 231 +/- 31 mg/min and energy expenditure changed by + 0.476 +/- 0.080, +0.293 +/- 0.095, -0.114 +/- 0.063, and +0.135 +/- 0.082 kJ/min in group I, II, IIIa, and IIIb, respectively. The increased energy expenditure correlated with glucose storage (measured cost of processing the glucose: 1.33 kJ/g). In group IIIa there was no increase in energy expenditure in response to glucose and insulin infusions. After therapy (group IIIb) there was a significant recovery (P less than 0.05) of the thermic effect of infused glucose although total glucose disposal was unchanged. It is proposed that the recovered thermic effect of infused insulin/glucose is due to the different contributions of gluconeogenesis in the fasting state and during the glucose clamp before and after weight loss. In addition we hypothesize that some of the lower thermic effect of food reported in obese noninsulin-dependent diabetics may be explained by decreased energy expenditure due to a greater suppression of hepatic gluconeogenesis as well as by lower storage rate.
Italian court edict over discharge rules causes controversy
Authors: M. Day
Journal: BMJ (2011)

Italy’s highest court has ruled that doctors who discharge patients to save money are breaking the law. As a result of the decision one doctor is now facing a manslaughter conviction.

The Court of Cassation’s ruling relates to the case of an angioplasty recipient who died on the night of his discharge nine days after the procedure.

The doctor who ordered his discharge from the hospital in Busto Arsizio, near Milan, in June 2004 claimed that the patient, an obese smoker who had had a heart attack, had stabilised and that the release adhered to hospital guidelines. …
Congenital rubella in babies of south Asian women in England and Wales.
Authors: C M Crawford
Journal: BMJ (1987)

sion.Furthermore, before the Wendy Savage case a doctor was never able to vindicate himself or herself publicly because hearings under the HM (61)112 procedure were held in secret.Fortunately, the High Court decreed that "the maxim that 'justice must not only be done but must manifestly be seen to be done' applies in full measure" to the 190 procedure (judgment of 21 July 1986).'
DNA Synthesis and Mitoses in Coronary Collateral Vessels of the Dog
Authors: WOLFGANG SCHAPER, MARC DE BRABANDER, PAUL LEWI
Journal: Circulation Research (1971)

DNA synthesis and mitotic activity in coronary collateral arterioles was assessed in dogs at different time intervals after gradual ameroid constriction of the left circumflex coronary artery. Labeling of nuclei and the mitotic index were highest at 3 weeks after implantation of the constrictor and gradually declined thereafter. Labeling persisted for at least 8 weeks but radioactive DNA was not found 12 months after coronary artery constriction nor in controls or animals with sham operations. Proliferative activity was, at any time interval, highest at the level of the smallest diameters of the collateral vessels. Labeled nuclei and mitoses were found in endothelial, medial, and adventitial cells. Myocardial mesenchymal cells also incorporated tritiated thymidine. The data provide evidence that after constriction of a major coronary artery, the coronary collateral vessels enlarge by an active growth process that follows the basic laws of cell kinetics.
Abstract LB-70: BRCA1 impacts ovarian cancer cell migration through modulating Pfn1 expression
Authors: David M. Gau, Jamie Lesnock, Thomas Krivak, Robert Edwards, Partha Roy
Journal: Cancer Research (2014)

Abstract Functional loss of BRCA1 has been implicated in genomic instability and cancer progression. A recent study demonstrated that BRCA1 plays a role in cancer cell migration. Using a random cell motility assay, we showed that BRCA1 promotes ovarian cancer cell migration. A proteomics study of BRCA1 +/- cell lines and tissues identified Profilin1 (Pfn1) as one of the differentially expressed proteins. This was further confirmed by Western blot and IHC analyses with tissue samples and cell lines. Pfn1 is an actin cytoskeleton-associated protein which promotes breast cancer cell motility/invasion and dissemination when downregulated. To further study whether BRCA1 impacts cell migration through Pfn1, Pfn1 was silenced which revealed enhanced motility in multiple BRCA1-WT ovarian cancer cell lines. Furthermore, overexpression of Pfn1 in BRCA1 cell lines reduced random motility which further implicates the importance of Pfn1 in ovarian cancer motility. This is the first evaluation of both motility and the functional role of Pfn1 in ovarian cancer cells. While BRCA1 has been extensively studied in the context of DNA repair, there is emerging evidence that BRCA1 proteins may play a role in cell migration. The increased motility seen in wild-type cells compared to BRCA1-mutated cells may portend increased metastatic potential in wild-type cancers. Our findings demonstrate that 1) BRCA1 positively influences ovarian cancer cell motility, and 2) BRCA1 status determines Pfn1's role in ovarian cancer cell motility suggesting a possible novel mechanism association between Pfn1 and BRCA1 and ovarian cancer cell motility. Future studies should explore whether Pfn1 downregulation enhances the metastatic potential of ovarian cancer cells with intact BRCA1 function and whether Pfn1 may serve as a possible therapeutic target. Citation Format: David M. Gau, Jamie Lesnock, Thomas Krivak, Robert Edwards, Partha Roy. BRCA1 impacts ovarian cancer cell migration through modulating Pfn1 expression. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-70. doi:10.1158/1538-7445.AM2014-LB-70