tbuckley/cabot-search huggingface dataset:
Abstract 5469: Pharmacokinetics and activity of nanoliposomal irinotecan (MM-398) against Ewings Sarcoma xenografts are superior to the conventional irinotecan formulation
Authors: Jing Wang, Rupeng Zhuo, Daryl Drummond, C. Patrick Reynolds, Min H. Kang
Journal: Cancer Research (2011)

Abstract Background: Irinotecan (CPT-11) is an antineoplastic prodrug, of which SN-38 is an active metabolite. Liposomal CPT-11 was developed to improve systemic and tumor exposure to CPT-11 and its active metabolite by reducing the exposure of CPT-11 to neutral and basic pH, in which CPT-11 is hydrolyzed into an inactive carboxylate form. The aims of the current study are 1) to compare the plasma and tissue/tumor pharmacokinetics of nanoliposomal CPT-11 (in clinical trials as PEP02 or MM-398) and conventional irinotecan in mice, and 2) to compare anti-tumor activity of the two formulations against Ewings Sarcoma murine xenografts. Methods: An assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to measure CPT-11 and SN-38 concentrations in plasma and tissue. Plasma and tissue pharmacokinetics of liposomal and conventional irinotecan were characterized in Balb/c mice (non-tumor bearing); pharmacokinetics and activity were assessed in athymic nu/nu mice xenografted with human Ewings sarcoma. Results: Following a 20 mg/kg dose of intravenous liposomal irinotecan, both plasma and tumor concentrations of CPT-11 and SN-38 were approximately 10-fold higher than conventional irinotecan. The Cmax and AUC were dose-proportionally increased after a single dose of liposomal irinotecan in non-tumor bearing mice. In mice xenografted with Ewings sarcoma (CHLA-258), liposomal irinotecan significantly extended event-free survival of mice compared with controls or conventional irinotecan (P&amp;lt;0.05). Conclusions: Our data demonstrate that 1) liposomal CPT-11 achieves higher plasma and tissue concentrations with longer duration compared with conventional irinotecan, and that 2) liposomal formulation has greater anti-tumor activity relative to conventional irinotecan. These results suggest that liposomal irinotecan may provide improved anti-tumor activity over conventional irinotecan by increasing systemic and tumor exposures to the SN-38 active metabolite. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5469. doi:10.1158/1538-7445.AM2011-5469
The Nitric Oxide Synthase/ Nitric Oxide and Heme Oxygenase/ Carbon Monoxide Pathways in the Human Ureter
Authors: C.E. Iselin, L. Ny, B. Larsson, N.C. Schaad, P. Alm, P. Graber, D.R. Morel, K.E. Andersson
Journal: European Urology (1998)
Exercise-induced Pulmonary Hypertension
Authors: Robert Naeije, Rebecca Vanderpool, Bishnu P. Dhakal, Rajeev Saggar, Rajan Saggar, Jean-Luc Vachiery, Gregory D. Lewis
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Exercise stresses the pulmonary circulation through increases in cardiac output (.Q) and left atrial pressure. Invasive as well as noninvasive studies in healthy volunteers show that the slope of mean pulmonary artery pressure (mPAP)-flow relationships ranges from 0.5 to 3 mm Hg.min.L(-1). The upper limit of normal mPAP at exercise thus approximates 30 mm Hg at a .Q of less than 10 L.min(-1) or a total pulmonary vascular resistance at exercise of less than 3 Wood units. Left atrial pressure increases at exercise with an average upstream transmission to PAP in a close to one-for-one mm Hg fashion. Multipoint PAP-flow relationships are usually described by a linear approximation, but present with a slight curvilinearity, which is explained by resistive vessel distensibility. When mPAP is expressed as a function of oxygen uptake or workload, plateau patterns may be observed in patients with systolic heart failure who cannot further increase .Q at the highest levels of exercise. Exercise has to be dynamic to avoid the increase in systemic vascular resistance and abrupt changes in intrathoracic pressure that occur with resistive exercise and can lead to unpredictable effects on the pulmonary circulation. Postexercise measurements are unreliable because of the rapid return of pulmonary vascular pressures and flows to the baseline resting state. Recent studies suggest that exercise-induced increase in PAP to a mean higher than 30 mm Hg may be associated with dyspnea-fatigue symptomatology.
Protective Efficacy of a Recombinant DNA Hepatitis B Vaccine in Neonates of HBe Antigen—Positive Mothers
Authors: Yong Poovorawan
Journal: JAMA (1989)

We have assessed the protective efficacy of a recombinant DNA hepatitis B vaccine alone in infants of women who were positive for the surface antigen and the e antigen. The infants received a 10-μg dose of the vaccine within 12 hours of birth and additional doses 1, 2, and 12 months later. No significant adverse reactions to vaccination were observed and the vaccine was highly immunogenic. Only 2 (3.6%) of the 55 infants followed up to 13 months became chronically infected with the hepatitis B virus, as evidenced by the persistent presence of hepatitis B surface antigen in serum samples. Without immunoprophylaxis, 65% to 90% of such infants would become chronic carriers. Immunization with a recombinant vaccine without concomitant administration of hepatitis B immunoglobulin, therefore, considerably decreased the incidence of the carrier state. (<i>JAMA</i>. 1989;261:3278-3281)
Career Satisfaction Among Physicians
Authors: B. E. Landon
Journal: JAMA (2004)

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
A rat strain that spontaneously develops severe hepatic necrosis and later hepatocellular carcinoma
Authors: Kunio Okuda
Journal: Hepatology (1988)

A new mutant causing hereditary hepatitis associated with severe jaundice has been discovered in the LEC strain of rats. Hepatitis appears suddenly in adult rats three to four months after birth. The clinical signs of hepatitis are characterized by severe jaundice, subcutaneous bleeding, oliguria, and loss of body weight. The affected rats showed a high lethality and histological changes of the liver with focal necrosis of enlarged hepatocytes without inflammatory cell response. Genetic tests indicate that at least a single autosomal recessive gene is responsible for the major cause of hepatitis. Furthermore, liver cancer appears in long survived rats after recovery from jaundice as well as a few asymptomatic rats without jaundice. The LEC rats thus provide an animal model useful for the basic and clinical studies of hepatitis and liver cancer, including their pathogenesis, prevention, and treatment.
Splenic function in adult coeliac disease.
Authors: P N Trewby, J S Stewart
Journal: Gut (1983)

SpJenic function in adult coeliac disease Sir, Corazza and colleagues' suggest that splenic function, as measured by the pitted red cell test, may improve in the short term after treatment with a gluten-free diet.As they point out this was not our experience in the longer term usinzg different tests of splenic function and splenic area.Nor, in fact, was it the experience of Corazza et al in an earlier study using the same pitted red cell test.3They showed that 44% of patients with the same mean age as patients described in their present study had evidence of splenic hypofunction, a mean of 3.8 years after starting on a gluten-free diet.Whatever changes may occur immediately after starting a gluten-free diet, their previous data support our conclusion that splenic hypofunction and splenic atrophy persist in patients after many years on a strict gluten-free diet.The practical implication stands: Howell-Jolly bodies in the peripheral blood film of patients with adult coeliac disease cannot be used as evidence of poor dietary compliance.
THE EXCRETION OF ZINC IN HEALTH AND DISEASE
Authors: Lawrence T. Fairhall, Lyman H. Hoyt
Journal: Journal of Clinical Investigation (1929)

During recent years increasing attention has been directed towards the occurrence of zinc as a normal constituent of animal tissues and fluids (1).Its wide distribution in foodstuffs and particularly its concentration in germ cells-the endosperm of wheat and the yolk of eggs, for example-and constant presence in milk points to a definite utilization.The fact that there is a more or less definite ratio of zinc to calcium in blood in the proportion of 7:100, and that zinc metabolism in animals has been shown to bear some relation to inorganic salt metabolism in general (2), leads to speculation as to the part it plays in the human organism.For this reason it was felt desirable to secure further data regarding the excretion of absorbed zinc under conditions of disease as compared with the normal.It is interesting to note that man ingests in his food practically as much zinc as he does iron.Far the greater part is excreted through the intestine.A small amount, however, is absorbed and excreted through the urine and, as the latter is a better index of absorbed zinc, a series of analyses of urinary zinc under conditions of health and disease was carried out.EXPERIMENTAL Twenty-four-hour specimens of urine were collected from a number of healthy individuals and also from hospital patients suffering from various diseases such as nephritis, uremia, duodenal ulcer, tuberculosis and diabetes.In order to avoid incidental contamination with zinc from glassware, the urine was collected in Pyrex glass-stoppered bottles and evaporated to dryness and ashed in Pyrex dishes.The zinc was separated and determined by a turbidimetric method as the ferrocyanide (3).
Access to records for epidemiological research.
Authors: D. Black
Journal: BMJ (1992)

feasible, it could be judged irresponsible not to do so owing to the risk to health of not getting regular exercise.Given proper provision for it, for the great majority of the population cycling as part of the routine of daily travel has the potential for improving fitness in a way that cannot be matched by any other comparable exercise regime-for instance, the report shows that there is only one public swimming bath for every 45 000 people in Britain.
Abstract P2-07-02: A novel megadeletion mouse model for mechanistic studies on the 8q24 non-coding breast cancer susceptibility locus
Authors: BMG Smits, MN Gould
Journal: Cancer Research (2013)

Abstract Genome-wide association studies (GWAS) have identified over 80 variants associated with breast cancer susceptibility. These loci have low-penetrance and are common in the population. Some of the alleles are associated with specific types of breast cancer, and/or associate differentially between certain ancestral populations. The vast majority of common, low-penetrance breast cancer susceptibility variants are located in non-protein coding genomic regions. It is hypothesized that the polymorphisms along the risk-associated alleles alter regulatory elements to modulate gene expression regulation. How such gene regulatory effects affect the susceptibility to breast cancer is completely unknown. To begin to study in vivo mechanisms underlying such non-protein coding breast cancer-associated loci, novel mammalian genetic models are indispensable. A prototype non-coding breast cancer susceptibility locus is the gene desert (i.e. a large genomic region devoid of known protein-coding genes) on human chromosomal band 8q24. The gene desert is flanked by MYC, PVT1 and FAM84b. It harbors 2 common, low-penetrance breast cancer susceptibility variants. We developed a novel megadeletion mouse model lacking a 450-Kb non-coding region orthologous to the breast cancer-associated 8q24 gene desert region. Mice homozygous for the megadeletion are viable. Analysis of the transcript levels of the flanking genes reveal organ-specific effects of the megadeletion mutation. Through genetic crosses with well-known transgenic mouse breast cancer models, we will examine the region's effect on mammary cancer multiplicity, size, latency and metastasis. Additional phenotyping and gene expression analysis will reveal novel insight in the mechanisms underlying this non-protein coding breast cancer-associated gene desert locus. The conclusions will extend beyond the 8q24 locus and will aid in understanding the influence of common, low-penetrance breast cancer loci in the etiology of breast cancer. [The mouse model was generated with help from University of Wisconsin Paul P. Carbone Comprehensive Cancer Center funds. The work is supported by a DoD MUSC-Baylor BRIDGE scholarship awarded to BMGS]. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-07-02.
Opsonization of bacteroides by the alternative complement pathway reconstructed from isolated plasma proteins.
Authors: A B Bjornson, P I Magnafichi, R D Schreiber, H S Bjornson
Journal: The Journal of Experimental Medicine (1987)

Opsonization of clinical isolates of B. fragilis and B. thetaiotaomicron with the six isolated proteins of the alternative complement pathway under physiological conditions resulted in considerable C3 deposition on the bacterial surfaces. The time course of C3 deposition was similar to that observed in EGTA-serum; however, the magnitude of C3 deposition was twofold greater in EGTA-serum. Opsonization of the bacteria with the isolated alternative pathway proteins failed to promote adherence, uptake, or killing by polymorphonuclear leukocytes, whereas opsonization of the bacteria with EGTA-serum facilitated these events. The difference in opsonic capacity of isolated proteins and EGTA-serum was not related to the quantitative difference in C3 deposition, because repeated opsonization of the bacteria with isolated proteins resulting in C3 deposition comparable to that observed in EGTA-serum only minimally increased adherence of the bacteria to polymorphonuclear leukocytes. SDS-PAGE and autoradiographic analysis of C3 extracted from bacteria opsonized with isolated proteins or EGTA-serum using methylamine and SDS demonstrated that the predominant form of C3 bound by ester bonds under both sets of conditions was iC3b. A low molecular weight C3 cleavage fragment was detected in extracts from bacteria opsonized with isolated proteins, but it accounted for only a minor fraction of the bound C3. The results of our study demonstrate that the early phase of opsonization involving activation of the alternative pathway by B. fragilis and B. thetaiotaomicron and resultant C3 deposition on the bacterial surfaces does not require auxiliary serum factors, but the effector phase of opsonization of these bacteria involving recognition of bacteria-bound C3 by polymorphonuclear leukocytes and the induction of phagocytosis and intracellular killing is dependent on such factors. Natural IgM antibodies serve as auxiliary factors is opsonization of B. thetaiotaomicron by the alternative pathway, whereas additional serum factors are required for alternative pathway-mediated opsonization of B. fragilis.
The Truth About Where You Live: An Atlas for Action on Toxins and Mortality
Authors: Andrew M. Davis
Journal: JAMA (1992)

There are large geographic variations in the United States for many measures of health and hundreds of superficially plausible socioeconomic, behavioral, genetic, and environmental factors that may account for these differences. This year marks the 30th anniversary of Rachel Carson's landmark condemnation of DDT,<i>Silent Spring</i>, and grassroots environmental activism shows no sign of abating. The past decade has fueled the trend with horrific industrial disasters, rapid growth of "right-toknow" laws, ready individual access to powerful computer databases, and growing citizen and media reluctance to defer to "the experts." Into this combustible mixture plunges Benjamin Goldman's provocative book<i>The Truth About Where You Live</i>, which embodies the promise and problems of citizen activism on issues of environmental health. Goldman has spent the past five years building a database, largely from US Environmental Protection Agency information and death certificate data, adjusted for age, sex, and race. Using over 100 computer-generated maps,
Side-by-Side Comparison of Lentivirally Transduced and mRNA-Electroporated Dendritic Cells: Implications for Cancer Immunotherapy Protocols
Authors: Melissa Dullaers, Karine Breckpot, Sonja Van Meirvenne, Aude Bonehill, Sandra Tuyaerts, Annelies Michiels, Lieven Straetman, Carlo Heirman, Catherine De Greef, Pierre Van Der Bruggen, Kris Thielemans
Journal: Molecular Therapy (2004)

The use of tumor antigen-loaded dendritic cells (DC) is one of the most promising approaches to inducing a tumor-specific immune response. We compared electroporation of mRNA to lentiviral transduction for the delivery of tumor antigens to human monocyte-derived and murine bone marrow-derived DC. Both lentiviral transduction and mRNA electroporation induced eGFP expression in on average 81% of human DC. For murine DC, eGFP mRNA electroporation (62%) proved to be more efficient than lentiviral transduction (47%). When we used tNGFR as a transgene we observed lentiviral pseudotransduction that overestimated lentiviral efficiency. Neither gene transfer method had an adverse effect on viability, phenotype, or allostimulatory capacity of either human or murine DC. Yet, the mRNA-electroporated DC showed a reduced production of IL-12p70 compared to their lentivirally transduced and unmodified counterparts. Human Ii80MAGE-A3-modified DC and murine Ii80tOVA-modified DC were able to present antigenic epitopes in the context of MHC class I and class II. Both types of modified murine DC were able to induce OVA-specific cytotoxic T cells in vivo; however, the mRNA-electroporated DC were less potent. Our data indicate that this may be related to their impaired IL-12 production. The use of tumor antigen-loaded dendritic cells (DC) is one of the most promising approaches to inducing a tumor-specific immune response. We compared electroporation of mRNA to lentiviral transduction for the delivery of tumor antigens to human monocyte-derived and murine bone marrow-derived DC. Both lentiviral transduction and mRNA electroporation induced eGFP expression in on average 81% of human DC. For murine DC, eGFP mRNA electroporation (62%) proved to be more efficient than lentiviral transduction (47%). When we used tNGFR as a transgene we observed lentiviral pseudotransduction that overestimated lentiviral efficiency. Neither gene transfer method had an adverse effect on viability, phenotype, or allostimulatory capacity of either human or murine DC. Yet, the mRNA-electroporated DC showed a reduced production of IL-12p70 compared to their lentivirally transduced and unmodified counterparts. Human Ii80MAGE-A3-modified DC and murine Ii80tOVA-modified DC were able to present antigenic epitopes in the context of MHC class I and class II. Both types of modified murine DC were able to induce OVA-specific cytotoxic T cells in vivo; however, the mRNA-electroporated DC were less potent. Our data indicate that this may be related to their impaired IL-12 production.
OPERATIVE TREATMENT OF CANCER OF THE STOMACH
Authors: WILLIAM J. MAYO
Journal: JAMA (1913)

The surgical treatment of cancer of the stomach compares favorably in results with the treatment of cancer of any other organ in the human body. When it is taken into consideration that nearly one-third of all cancers occur in the stomach and that their early discovery is a necessary factor in the cure of the disease, the necessity for a clear conception of the value of the various signs and symptoms is at once manifest. With the hope of obtaining some definite information on these important points, an investigation was made in our clinic of the histories of a thousand patients submitted to operation for cancer of the stomach. These operations were performed between Jan. 1, 1894, and Dec. 31, 1912. For purposes of study they have been classified as follows: resections, 378; palliative operations, 246; explorations, 376. The diagnosis of cancer of the stomach cannot often be made early
CAN THYROGLOBULIN MEASUREMENTS REPLACE r-131 SCANS IN THE FOLLOWUP OF THYROID CANCER PATIENTS?
Authors: Lalitha Ramanna, Alan Waxman, Nancy Sensel, Michael Brachman, Doina Tanasescu, Daniel Berman, Glenn Braunstein
Journal: Clinical Nuclear Medicine (1983)

Ramanna, Lalitha; Waxman, Alan; Sensel, Nancy; Brachman, Michael; Tanasescu, Doina; Berman, Daniel; Braunstein, Glenn Author Information
Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new algorithms are more precise and entirely noninvasive
Authors: Jérôme Boursier, Victor de Ledinghen, Jean-Pierre Zarski, Isabelle Fouchard-Hubert, Yves Gallois, Frédéric Oberti, Paul Calès
Journal: Hepatology (2011)

The sequential algorithm for fibrosis evaluation (SAFE) and the Bordeaux algorithm (BA), which cross-check FibroTest with the aspartate aminotransferase-to-platelet ratio index (APRI) or FibroScan, are very accurate but provide only a binary diagnosis of significant fibrosis (SAFE or BA for Metavir F ≥ 2) or cirrhosis (SAFE or BA for F4). Therefore, in clinical practice, physicians have to apply the algorithm for F ≥ 2, and then, when needed, the algorithm for F4 ("successive algorithms"). We aimed to evaluate successive SAFE, successive BA, and a new, noninvasive, detailed classification of fibrosis. The study included 1785 patients with chronic hepatitis C, liver biopsy, blood fibrosis tests, and FibroScan (the latter in 729 patients). The most accurate synchronous combination of FibroScan with a blood test (FibroMeter) provided a new detailed (six classes) classification (FM+FS). Successive SAFE had a significantly (P < 10(-3) ) lower diagnostic accuracy (87.3%) than individual SAFE for F ≥ 2 (94.6%) or SAFE for F4 (89.5%), and required significantly more biopsies (70.8% versus 64.0% or 6.4%, respectively, P < 10(-3) ). Similarly, successive BA had significantly (P ≤ 10(-3) ) lower diagnostic accuracy (84.7%) than individual BA for F ≥ 2 (88.3%) or BA for F4 (94.2%), and required significantly more biopsies (49.8% versus 34.6% or 24.6%, respectively, P < 10(-3) ). The diagnostic accuracy of the FM+FS classification (86.7%) was not significantly different from those of successive SAFE or BA. However, this new classification required no biopsy.SAFE and BA for significant fibrosis or cirrhosis are very accurate. However, their successive use induces a significant decrease in diagnostic accuracy and a significant increase in required liver biopsy. A new fibrosis classification that synchronously combines two fibrosis tests was as accurate as successive SAFE or BA, while providing an entirely noninvasive (0% liver biopsy) and more precise (six versus two or three fibrosis classes) fibrosis diagnosis.