tbuckley/cabot-search huggingface dataset:
Concepts, labeling procedures, and design of cell proliferation studies relating to carcinogenesis.
Authors: T L Goldsworthy, B E Butterworth, R R Maronpot
Journal: Environmental Health Perspectives (1993)

Chemicals may induce cell proliferation directly as mitogens or indirectly via cell death with subsequent proliferation to replace lost cells. Chemically induced proliferation has been demonstrated to play a role in the carcinogenic process. A wide range of procedures and techniques are currently being used to define the quantitative relationship between the extent and duration of chemically induced cell proliferation and carcinogenic potential in different species and target organs. However, a limited database and nonstandard protocols and procedures for measuring cell proliferation have made it difficult to compare results between laboratories. Comparison of frequencies of S phase between control and treated animals is the most commonly used end point in cell proliferation studies and may be regarded as an indirect indication of a proliferative response. This response can be ascertained as labeling indexes (LI; percentage of cells in S phase) after the administration of the DNA precursor labels (tritiated thymidine; 3H-TdR; bromodeoxyuridine, BrdU) or through immunostaining of the endogenous cell replication marker, proliferating cell nuclear antigen (PCNA). Both approaches are applicable to tissue sections. An important issue in the design of experimental studies for measuring LI is determining how and when to investigate proliferative responses in relation to the chemical treatment regimen. Variables to consider when designing cell proliferation studies include the animal's age, chemical dose and method of treatment, choice and dose of label, time and length that the label is administered, and methods of quantitation.(ABSTRACT TRUNCATED AT 250 WORDS)
Arcus Senilis and Serum Cholesterol Levels in the Aleut
Authors: Stanley Marion Garn, Menard M. Gertler
Journal: New England Journal of Medicine (1950)

ARCUS senilis is considered to be one of the stigmas of age not only in European whites but also in persons of all racial groups. In recent years investigators have become interested in determining what aspects of aging are responsible for arcus senilis, and they have reported a higher frequency of appearance in arteriosclerosis, hypertension, diabetes, xanthomatosis, and other disorders in which metabolic abnormalities superimpose premature aging.Recently, Boas et al.1 2 3 4 have devoted considerable attention to arcus senilis in relation to disorders of cholesterol metabolism, and they have demonstrated a higher incidence in persons with hypercholesterolemia, as well as noting . . .
Vaccines and Vaccination
Authors: Gordon Ada
Journal: New England Journal of Medicine (2001)

More than 70 bacteria, viruses, parasites, and fungi are serious human pathogens.1 Vaccines are available against some of these agents and are being developed against almost all the other bacteria and viruses and about half of the parasites. Table 1 lists infections for which there are now licensed vaccines and those for which a candidate vaccine has undergone a phase 3 clinical trial,2 indicating that a vaccine will probably be licensed within 5 to 10 years.Traditionally, attenuated vaccines were made by repeated passaging of the infectious agent in tissue culture or animal hosts until its virulence was greatly decreased but its . . .
Platelet‐induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera
Authors: Marina Panova‐Noeva, Marina Marchetti, Henri Maria Spronk, Laura Russo, Erika Diani, Good Finazzi, Silvia Salmoiraghi, Aueesandrd Rambaldi, Titiano Barbui, Huao Ten Cate, Anna Falanga
Journal: American Journal of Hematology (2011)

Abstract The platelet contribution to the thrombophilic state of patients with myeloproliferative neoplasms (MPNs), i.e., essential thrombocythemia (ET) and polycythemia vera (PV), remains uncertain. In this study we aimed to characterize the thrombin generation (TG) potential expressed by platelets from these subjects, compare it to normal platelets, and identify what factors might be responsible for platelet TG. In a group of 140 MPN patients (80 ET and 60 PV) and 72 healthy subjects we measured the global procoagulant potential of platelet rich plasma (PRP) utilizing the TG assay by the calibrated automated thrombogram (CAT). To characterize the procoagulant contribution of platelets in PRP, the TG of both isolated platelets and platelet poor plasma was measured, and the platelet surface expression of TF was determined. Finally, the activation status of platelets was assessed by the levels of P‐selectin expressed on platelet surface. MPN patients had significantly increased PRP and isolated platelet TG potential compared to controls. This was associated to the occurrence of platelet activation. Patients carriers of the JAK2V617F mutation showed the highest values of TG and platelet surface TF and P‐selectin. Platelet TG potential was significantly lower in hydroxyurea (HU) compared to non‐HU‐treated patients and was lowest in HU‐treated JAK2V617F carriers. In subjects not receiving HU, platelet TG significantly increased by JAK2V617F allele burden increment ( P &lt; 0.05). This study demonstrates a platelet‐dependent form of hypercoagulability in MPN patients, particularly in those carriers of the JAK2V617F mutation. The cytoreductive therapy with HU significantly affects this prothrombotic phenotype. Am. J. Hematol. 86:337–342, 2011. © 2011 Wiley‐Liss, Inc.
Enhanced insulin response relates to acetylcholine-induced vasoconstriction in vasospastic angina
Authors: Michio Shimabukuro, Tatsushi Shinzato, Satoshi Higa, Takao Chibana, Hisashi Yoshida, Fumio Nagamine, Keiji Murakami, Nobuyuki Takasu
Journal: Journal of the American College of Cardiology (1995)
Identification of Grb2 As a Novel Binding Partner of Tumor Necrosis Factor (TNF) Receptor I
Authors: Eberhard Hildt, Stefanie Oess
Journal: The Journal of Experimental Medicine (1999)

Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine. Its pleiotropic biological properties are signaled through two distinct cell surface receptors: the TNF receptor type I (TNFR-I) and the TNF receptor type II. Neither of the two receptors possesses tyrosine kinase activity. A large majority of TNF-α–dependent activities can be mediated by TNFR-I. Recently, c-Raf-1 kinase was identified as an intracellular target of a signal transduction cascade initiated by binding of TNF-α to TNFR-I. However, the mechanism engaged in TNF-α–dependent activation of c-Raf-1 kinase is still enigmatic. Here we report that the cytosolic adapter protein Grb2 is a novel binding partner of TNFR-I. Grb2 binds with its COOH-terminal SH3 domain to a PLAP motif within TNFR-I and with its NH2-terminal SH3 domain to SOS (son of sevenless). A PLAP deletion mutant of TNFR-I fails to bind Grb2. The TNFR-I/Grb2 interaction is essential for the TNF-α–dependent activation of c-Raf-1 kinase; activation of c-Raf-1 kinase by TNF-α can be blocked by coexpression of Grb2 mutants harboring inactivating point mutations in the NH2- or COOH-terminal SH3 domain, cell-permeable peptides that disrupt the Grb2/TNFR-I interaction or transdominant negative Ras. Functionality of the TNFR-I/Grb2/SOS/Ras interaction is a prerequisite but not sufficient for TNF-α–dependent activation of c-Raf-1 kinase. Inhibition of the TNFR-I/FAN (factor associated with neutral sphingomyelinase) interaction, which is essential for TNF-α–dependent activation of the neutral sphingomyelinase, either by cell-permeable peptides or by deletion of the FAN binding domain, prevents activation of c-Raf-1 kinase. In conclusion, binding of the Grb2 adapter protein via its COOH-terminal SH3 domain to the nontyrosine kinase receptor TNFR-I results in activation of a signaling cascade known so far to be initiated, in the case of the tyrosine kinase receptors, by binding of the SH2 domain of Grb2 to phosphotyrosine.
Prevalence of Latex-Specific IgE Antibodies in Atopic and Nonatopic Children With Type I Diabetes
Authors: Thomas Danne, Bodo Niggemann, Bruno Weber, Ulrich Wahn
Journal: Diabetes Care (1997)

OBJECTIVE The potential induction of allergic sensitization to latex from insulin vial tops stimulated an investigation of the prevalence of specific IgE antibodies to latex in serum and the relationship to atopic disease in children with diabetes. RESEARCH DESIGN AND METHODS In a cross-sectional study, serum samples of 112 children with type I diabetes (age: 15 [5–18] years; diabetes duration: 6 [1–14] years; median [range]) were investigated for total IgE, IgE screening for inhalational and nutritional allergens, and specific IgE antibodies to latex. RESULTS Specific IgE antibodies for inhalational and/or nutritional allergens was found in 42 (38%) children (atopic group). Seven children (6%) exhibited specific IgE antibodies (0.61 [0.40–3.84] kU/I) to latex in serum although none reported clinical symptoms of latex allergy. All latex-sensitized children were found in the atopic group. This prevalence of latex sensitization of 17% (7/42) in atopic children with diabetes is comparable with the frequency described in atopic children without diabetes. These seven patients had higher serum total IgE antibody levels (328 [113–1,000] kU/I) than atopic patients without latex sensitization (n = 35; 124 [24–857] kU/I; P &amp;lt; 0.05) or patients without atopy (n = 70; 33 [2–339] kU/I; P &amp;lt; 0.001). No differences in age or diabetes duration were observed between either group. CONCLUSIONS Sensitization to latex is found exclusively in children with atopic sensitization and appears to be related to atopic disease and not to frequent contact to latex through insulin injections. However, atopic patients may be at risk for reactions secondary to latex from insulin vials and syringes.
Impairment of CD4<sup>+</sup>cytotoxic T cells predicts poor survival and high recurrence rates in patients with hepatocellular carcinoma
Authors: Junliang Fu, Zheng Zhang, Lin Zhou, Zhaorui Qi, Shaojun Xing, Jiyun Lv, Jianfei Shi, Baoyun Fu, Zhenwen Liu, Ji-Yuan Zhang, Lei Jin, Yulai Zhao, George K.K. Lau, Jingmin Zhao, Fu-Sheng Wang
Journal: Hepatology (2012)

Abstract The role of CD4 + cytotoxic T cells (CTLs) in hepatocellular carcinoma (HCC) remains obscure. This study characterized CD4 + CTLs in HCC patients and further elucidated the associations between CD4 + CTLs and HCC disease progression. In all, 547 HCC patients, 44 chronic hepatitis B (CHB) patients, 86 liver cirrhosis (LC) patients, and 88 healthy individuals were enrolled in the study. CD4 + CTLs were defined by flow cytometry, immunohistochemistry, and lytic granule exocytosis assays. A multivariate analysis of prognostic factors for overall survival was performed using the Cox proportional hazards model. Circulating and liver-infiltrating CD4 + CTLs were found to be significantly increased in HCC patients during early stage disease, but decreased in progressive stages of HCC. This loss of CD4 + CTLs was significantly correlated with high mortality rates and reduced survival time of HCC patients. In addition, the proliferation, degranulation, and production of granzyme A, granzyme B, and perforin of CD4 + CTLs were inhibited by the increased forkhead/winged helix transcription factor (FoxP3 + ) regulatory T cells in these HCC patients. Further analysis showed that both circulating and tumor-infiltrating CD4 + CTLs were independent predictors of disease-free survival and overall survival after the resection of the HCC. Conclusion: The progressive deficit in CD4 + CTLs induced by increased FoxP3 + regulatory T cells was correlated with poor survival and high recurrence rates in HCC patients. These data suggest that CD4 + CTLs may represent both a potential prognostic marker and a therapeutic target for the treatment of HCC. (HEPATOLOGY 2013)
Kinetics of the human renin and human substrate reaction
Authors: A. B. Gould, D. Green
Journal: Cardiovascular Research (1971)

The Michaelis constant (Km) for the hydrolysis of human renin substrate by human renin is 0·931 n-mole/ml. This concentration of substrate is higher than that found in a normotensive population. Since the Km is numerically equal to the concentration of substrate that will permit the reaction to proceed at half its maximal velocity, substrate concentration in normal serum occurs at a very critical level.
Effects of the Differentiating Agent Hexamethylene Bisacetamide on Normal and Myelodysplastic Hematopoietic Progenitors
Authors: E. K. Rowinsky, R. C. Donehower, J. L. Spivak, P. J. Burke, C. A. Griffin, R. J. Jones
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Effects of the Differentiating Agent Hexamethylene Bisacetamide on Normal and Myelodysplastic Hematopoietic Progenitors Get access Eric K. Rowinsky, Eric K. Rowinsky * Division of Pharmacology and Experimental Therapeutics, The Johns Hopkins Oncology Center, The Johns Hopkins Medical InstitutionsBaltimore, Md. *Correspondence to : Eric K. Rowinsky, MD, The Johns Hopkins Oncology Center, 600 N Wolfe St, Room 1–121, Baltimore, MD 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ross C. Donehower, Ross C. Donehower Division of Pharmacology and Experimental Therapeutics, The Johns Hopkins Oncology Center, The Johns Hopkins Medical InstitutionsBaltimore, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Jerry L. Spivak, Jerry L. Spivak Department of Medicine, The Johns Hopkins Medical InstitutionsBaltimore, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Philip J. Burke, Philip J. Burke Adult Leukemia Program, The Johns Hopkins Oncology Center, The Johns Hopkins Medical InstitutionsBaltimore, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Constance A. Griffin, Constance A. Griffin Division of Pharmacology and Experimental Therapeutics, The Johns Hopkins Oncology Center, The Johns Hopkins Medical InstitutionsBaltimore, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard J. Jones Richard J. Jones Division of Bone Marrow Transplantation, The Johns Hopkins Oncology Center, The Johns Hopkins Medical InstitutionsBaltimore, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 24, 19 December 1990, Pages 1926–1931, https://doi.org/10.1093/jnci/82.24.1926 Published: 19 December 1990 Article history Received: 12 July 1990 Revision received: 26 September 1990 Accepted: 02 October 1990 Published: 19 December 1990
An egotistical and dictatorial style
Authors: Jeremy Hugh Baron
Journal: BMJ (2005)

Chronic inflammatory demyelinating polyneuropathy (CIDP) is probably the best-recognised progressive immune-mediated peripheral neuropathy. It presents with symmetrical, motor predominant peripheral neuropathy that produces both distal and proximal weakness. Here we report a case of a 38-year-old man who presented with chronic additive large and small joint inflammatory polyarthritis, associated with morning stiffness, anasarca associated with frothy urine and progressive episodic, relapsing and remitting, sensorimotor lower motor neuron type quadriparesis without any bladder and bowel involvement. He was diagnosed as a case of CIDP, and the aetiology was found out to be mixed connective tissue disorder, which is a rare association with CIDP. The patient responded dramatically to glucocorticoid.
Mast cell–derived TNF contributes to airway hyperreactivity, inflammation, and TH2 cytokine production in an asthma model in mice
Authors: Susumu Nakae, Lien H. Ho, Mang Yu, Rossella Monteforte, Motoyasu Iikura, Hajime Suto, Stephen J. Galli
Journal: Journal of Allergy and Clinical Immunology (2007)
Sustained Muscle Expression of Dystrophin from a High-Capacity Adenoviral Vector with Systemic Gene Transfer of T Cell Costimulatory Blockade
Authors: Zhilong Jiang, Gudrun Schiedner, Nico van Rooijen, Chau-Ching Liu, Stefan Kochanek, Paula R. Clemens
Journal: Molecular Therapy (2004)

Adenoviral vector (Ad)-mediated gene delivery of normal, full-length dystrophin to skeletal muscle provides a promising strategy for the treatment of Duchenne muscular dystrophy (DMD). However, cellular and humoral immune responses induced by vector gene transfer limit the application of this approach. Blockade of the costimulatory interaction between naïve T cells and antigen-presenting cells has proven to be a successful means to diminish immunity induced by gene transfer. In this study we explore the potential of supplementing dystrophin gene delivery to dystrophin-deficient Dmd mouse skeletal muscle with systemic gene delivery of CTLA4Ig and CD40Ig molecules to effect costimulatory blockade. We found that systemic administration of a high-capacity Ad (HC-Ad) vector carrying murine CTLA4Ig (AdmCTLA4Ig) either alone or codelivered with an HC-Ad vector carrying murine CD40Ig (AdmCD40Ig) provided sustained expression of recombinant full-length murine dystrophin from an HC-Ad vector carrying the dystrophin cDNA (AdmDys). The level of AdmDys vector genomes remained stable in animals cotreated with systemic delivery of vectors carrying molecules to block costimulation. In addition, muscle CD4+ and CD8+ T cell infiltrates and Th1 cytokine production by splenocytes were reduced. The production of neutralizing antibody against Ad vector was significantly inhibited in mice receiving systemic codelivery of both AdmCTLA4Ig and AdmCD40Ig, but not in the mice treated with AdmCTLA4Ig alone. The results suggested that coblockade of both CD28/B7 and CD40L/CD40 costimulatory pathways is required for effective inhibition of the Ad vector-induced humoral immune response in Dmd mice, whereas blockade of CD28/B7 alone by murine CTLA4Ig would be sufficient for prolonged dystrophin expression in treated muscle.
THE SYMPTOMS AND DIAGNOSIS OF STRANGULATION OF THE INTESTINE.
Authors: JOHN B. ROBERTS
Journal: JAMA (1907)

The development of the operative surgery of the abdomen has created in the minds of surgeons such an assurance of success that they are liable to neglect the study of diagnosis and to resort too cheerily to exploratory investigation of lesions in this cavity. Physicians, on the other hand, being more or less unfamiliar with the innocuousness of aseptic inspection of the abdominal contents, lose valuable time in fruitless efforts to overcome mechanical impediments to peristalsis. Patients would have a fuller measure of scientific aid in their dire extremity, if surgeons could profit by frequent opportunity to see cases of intestinal obstruction early enough to study initial symptoms. On the other hand, many lives would undoubtedly be saved, if physicians realized the futility of wasting time in the effort to settle diagnostic problems, when the fecal current and perhaps the blood circulation are stopped by mechanical causes, demanding instant manipulative
The PSRO in Perspective
Authors: Helen L. Smits
Journal: New England Journal of Medicine (1981)

The Reagan administration has proposed a three-year phase-out of the Professional Standards Review Organization (PSRO) program. The resulting debate in the 97th Congress is focusing on conservatives' concerns that the program represents an intrusion into medical practice rather than liberals' fears that physician-based organizations will not conduct rigorous review. There are three possible future directions for PSROs: rapid elimination through budget cuts; retention of some PSROs at current budget levels, which would essentially mean slow starvation; or retention of some PSROs, with major changes in their relation to the federal government. Multiple sources of funding and a linkage of local PSRO budgets to local effectiveness could further enhance the performance of the best PSROs. As national mechanisms of health-care financing change, the role of PSROs should also change; there is a central place for physician-based review in "pro-competitive" health-care-financing systems.
NIH Expands Access to Clinical Center
Authors: Bridget M. Kuehn
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
Monitoring and Evaluating Progress towards Universal Health Coverage in Brazil
Authors: Mauricio L. Barreto, Davide Rasella, Daiane B. Machado, Rosana Aquino, Diana Lima, Leila P. Garcia, Alexandra C. Boing, Jackson Santos, Juan Escalante, Estela M. L. Aquino, Claudia Travassos
Journal: PLoS Medicine (2014)

This paper is a country case study for the Universal Health Coverage Collection, organized by WHO. Mauricio Barreto and colleagues illustrates progress towards UHC and its monitoring and evaluation in Brazil. Please see later in the article for the Editors' Summary
Steven L Shafer responds to Jeanne Lenzer
Authors: S. L Shafer
Journal: BMJ (2010)

The radioactive material in urine after parenteral radioactive hydroxocobalamin is composed of radioactive cyanocobalamin, radioactive hydroxocobalamin, and a radioactive anionic complex. Studies <i>in vitro</i> suggest that these materials have a similar microbiological activity. Comparison of the amounts of radioactive and microbiologically active material in urine after parenteral radioactive hydroxocobalamin show a significant correlation both in the first and second 24 hours after injection showing that the amount of radioactivity is an acceptable measure of the loss of cobalamin in urine. The slope of the regression lines obtained from cobalamin-deficient and normal subjects implies that there is no equilibration of injected radioactive hydroxocobalamin and body stores: this may be due to the absence of hydroxocobalamin from tissues or to the fact that tissue hydroxocobalamin is bound and incapable of equilibration.