tbuckley/cabot-search huggingface dataset:
A chemical perspective on the anthracycline antitumor antibiotics.
Authors: B R Abdella, J Fisher
Journal: Environmental Health Perspectives (1985)

The anthracycline antitumor antibiotics occupy a central position in the chemotherapeutic control of cancer. They remain, however, antibiotics of the last resort and thus exhibit toxicity both to the neoplasm and to the host organism. As part of the continuing effort to dissociate the molecular processes responsible for these two separate toxicities, attention has been drawn to the intrinsic redox capacity of their tetrahydronapthacenedione aglycone moiety, and to the possible expression of this redox activity against those biomolecules for which anthracyclines have a particular affinity (polynucleotides and membranes). This review is a synopsis of the present trends and thoughts concerning this relationship, written from the point of view of the intrinsic chemical competence of the anthracyclines and their metabolites. While our ignorance is profound--the precise molecular locus of the antitumor expression of the anthracyclines remains unknown--there is now evidence that the relationship of the anthracyclines to the DNA (possibly requiring enzymatic cooperation) and to the membranes, with neither event requiring redox chemistry, may comprise the core of the antitumor effects. The adventitious expression of the redox activity under either aerobic conditions (in which circumstances molecular oxygen is reduced) or anaerobic conditions (in which circumstances potentially reactive aglycone tautomers are obtained) is therefore thought to contribute more strongly to the host toxicity. Yet little remains proven, and the understanding of the intrinsic chemical competence can do little more than lightly define the boundaries within which are found these and numerous other working hypotheses.
Abstract 3101: The Role of MYC and the miR-17∼92 cluster in histone deacetylase inhibitor-induced apoptosis.
Authors: Dominique R. Talbert, Robert L. Wappel, Diarmuid M. Moran, Scott A. Shell, Sarah S. Bacus
Journal: Cancer Research (2013)

Abstract In recent years histone deacetylase inhibitors (HDACi's) have emerged as promising therapeutics for cancer. While favorable responses to HDACi's as single agents have been shown in several hematological malignancies, very little efficacy has been demonstrated in solid tumors. c-Myc (Myc), an oncoprotein commonly over-expressed in cancer, has been shown by several studies to play a critical role in HDACi-mediated cellular death. To expand upon these findings and determine the role that Myc plays in this process in solid tumors, we compared the effect of two HDAC inhibitors, SAHA and LAQ824, on the proliferation of solid tumor cell lines expressing high versus low levels of Myc. We found that cells expressing high levels of Myc were more sensitive to HDACi. In addition, there were significant differences in the type of response to HDACi treatment between the two cell types with prominent apoptosis in cells expressing higher levels of Myc while cell cycle arrest was more commonly observed in cells expressing lower levels of Myc. Interestingly, HDACi reduced the expression of Myc and one of its well-known oncogenic miRNA targets, miR-17∼92 cluster, resulting in an increase in the expression of the master pro-apoptotic protein Bim. We propose that this novel mechanism may play a role in the potent anti-proliferative effects mediated by HDACi. Furthermore, these studies suggest that Myc expression could be used as a predictive biomarker to select patients with solid tumors who may be more responsive to HDACi treatment. Citation Format: Dominique R. Talbert, Robert L. Wappel, Diarmuid M. Moran, Scott A. Shell, Sarah S. Bacus. The Role of MYC and the miR-17∼92 cluster in histone deacetylase inhibitor-induced apoptosis. [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 3101. doi:10.1158/1538-7445.AM2013-3101 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Effect of Meal Frequency on Blood Glucose, Insulin, and Free Fatty Acids in NIDDM Subjects
Authors: Jette Bertelsen, Christian Christiansen, Claus Thomsen, Per L Poulsen, Svend Vestergaard, Alice Steinov, Lars H Rasmussen, Ole Rasmussen, Kjeld Hermansen
Journal: Diabetes Care (1993)

Objective— We studied the effects of meal frequency on blood glucose, serum insulin, and FFAs in 12 NIDDM subjects. Research Design and Methods— Subjects were assigned in random order to two 8-hr observation periods after an overnight fast. They received isocaloric diets with similar composition either as six small or as two large meals. At the end of each study period, an IVGTT was given. Results— Two large meals induced an 84% greater maximum amplitude of glucose excursions than six small meals (6.1 ± 0.5 vs. 3.3 ± 0.5 mM, P &amp;lt; 0.005) and higher insulin responses (P &amp;lt; 0.03). The Kg response to an IVGTT did not differ in the two situations. The average FFA level was lowest in response to frequent meals (P &amp;lt; 0.02). Conclusions— A higher meal frequency acutely subdues glucose excursions and reduces insulin and FFA levels during the daytime in older NIDDM subjects.
Pure red cell aplasia caused by D-penicillamine treatment of rheumatoid arthritis.
Authors: M Tishler, Y Kahn, M Yaron
Journal: Annals of the Rheumatic Diseases (1991)

A 40 year old woman with rheumatoid arthritis developed pure red cell aplasia after treatment with D-penicillamine 500 mg/day. D-Penicillamine was stopped and short term treatment with steroids resulted in complete recovery of bone marrow.
Contact Precautions for Patients With Multidrug-Resistant Pathogens—Reply
Authors: Daniel J. Morgan, Keith S. Kaye, Daniel J. Diekema
Journal: JAMA (2015)

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
COMPLEMENT AS A MEDIATOR OF INFLAMMATION
Authors: W. Dias da Silva, John W. Eisele, Irwin H. Lepow
Journal: The Journal of Experimental Medicine (1967)

Purified preparations of human C'1 esterase, C'4, C'2, C'3, and C'5 were labeled with (125)I. Reaction mixtures were prepared containing a single labeled component and other unlabled components. After incubation at 37 degrees C for 10 min at pH 7.4 in the presence of 5 x 10(-4)M Mg(2+), they were adjusted to pH 3.5 and subjected to sucrose density gradient ultracentrifugation and gel filtration at pH 3.5. In all cases, an activity capable of contracting guinea pig ileum with tachyphylaxis was obtained in low molecular weight fractions. However, these fractions were labeled only when (125)I-C'3 was employed, indicating that biological activity was associated with a cleavage product of C'3. This fragment has been designated F(a)C'3 in a nomenclature consistent with that of immunoglobulin degradation products. The much larger, residual portion of the C'3 molecule has been designated F(b)C'3. The biochemical characteristics of generation of F(a)C'3 were consistent with a mechanism involving action of C'1 esterase on C'4 and C'2, activation of C'2, and cleavage of C'3. F(a)C'3 had a molecular weight by gel filtration techniques of 6800 or less. It was thermostable and susceptible to inactivation by endo- and exopeptidases. The isolated fragment possessed all of the biological properties of unfractionated mixtures of C'1 esterase, C'4, C'2, and C'3. In addition to contraction of guinea pig ileum, these included failure to contract rat uterus, enhancement of vascular permeability in guinea pig skin, degranulation of mast cells in guinea pig mesentery, and release of histamine from rat peritoneal mast cells. F(a)C'3 did not cross-desensitize guinea pig ileum to rat agar anaphylatoxin and vice versa. The existence of different protein fragments with anaphylatoxin properties has been discussed. Distinctive characteristics of F(a)C'3 from classical anaphylatoxin generated by treatment of fresh rat serum with agar have been indicated.
The many faces of self-deception
Authors: Dennis Krebs, J'Anne Ward, Tim Racine
Journal: Behavioral and Brain Sciences (1997)

Those who invoke the word self-deception to represent one phenomenon often argue that those who use it to represent another are misusing the construct. Better to recognize that self-deception is a fuzzy concept that may be used to represent a variety of mental processes and states, and to direct our energy toward distinguishing empirically among its forms and functions.
Plasmacytoid dendritic cells lead the charge against tumors
Authors: Sonia Jiménez-Baranda, Inês Pires Silva, Nina Bhardwaj
Journal: Journal of Clinical Investigation (2012)

Imiquimod is a TLR agonist that is used as an antitumor agent, mainly against skin tumors. Its clinical benefits are well described in several studies; however, the mechanisms behind its antitumor effects are not completely understood. In this issue of the JCI, Drobits and colleagues demonstrate that topical application of imiquimod suppresses cutaneous melanoma by TLR7-dependent recruitment and transformation of plasmacytoid dendritic cells into killer cells; this occurs independently of conventional adaptive immune mechanisms.
ACC/AHA, Adult Treatment Panel III, and ESC guidelines overestimated risk for CVD in older adults
Authors: Prashant Vaishnava, Kim A. Eagle
Journal: Annals of Internal Medicine (2014)

Source Citation Kavousi M, Leening MJ, Nanchen D, et al. Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III guidelines, and European Society of Cardiology guidelines for cardiovascular disease prevention in a European cohort. JAMA. 2014;311:1416-23. 24681960
Heavy Particles in the Treatment of Acromegaly, Cushing's Disease, and Nelson's Syndrome.
Authors: John H. Lawrence
Journal: Annals of Internal Medicine (1972)

Meeting Abstracts1 May 1972Heavy Particles in the Treatment of Acromegaly, Cushing's Disease, and Nelson's Syndrome.John H. Lawrence, M.D., F.A.C.P.John H. Lawrence, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-859_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPituitary disorders, including acromegaly, Cushing's disease, Nelson's syndrome and chromophobe adenoma, have been treated with 910-Mev alpha particles. By using their special radiobiological properties the known resistance of the pituitary to conventional externally delivered radiations (X or gamma rays) has been overcome, and a sufficiently large amount of energy has been delivered to the hyperplastic or adenomatous pituitary without damaging surrounding vital structures and without entering the cranial cavity. During the past 14 years 153 patients with acromegaly were successfully treated, achieving a relief symptoms and signs and a return to normal of elevated growth hormone levels and of other... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Berkeley, Calif. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1972Volume 76, Issue 5Page: 859-859KeywordsAcromegalyAdenomasGrowth hormoneSigns and symptoms Issue Published: 1 May 1972 PDF DownloadLoading ...
Emergency Establishment Of Intravenous Route
Authors: Joseph J. Dodds
Journal: JAMA (1966)

ABSTRACT To the Editor:— A question concerning the direct administration of fluid into the bone marrow arose (196: 1101, 1966).In my experience, I have administered fluid, on three separate occasions, in this manner. Two of the patients had extensive burns of the four extremities, which prevented the use of peripheral veins. In these two cases, intravenous fluids, including electrolyte solutions and vitamins, as well as whole blood, were administered through a bonemarrow needle inserted into the marrow cavity of the sternum. In the other case, the peripheral routes of intravenous replacement were exhausted as a result of continuous long-term intravenous therapy, and in this case a bone-marrow needle was inserted into the iliac crest and fluid replacement was carried on through the iliac bone marrow. In all three of these patients, fluids ran well and no complications attributable to the route of administration arose.
A danger to health
Authors: G. M. Waine
Journal: BMJ (1995)

Mention Lady Killers to those of a certain generation and a film screened in the 1950s is immediately brought to mind. Granada Television had a much more serious aim in presenting a six part documentary series with the same title. The press release states that “the series looks at the major diseases that kill women” and “tackles serious subjects in a positive and optimistic way, covering each week's topic through the stories of celebrities and ordinary families that have been affected.” The selected topics--cervical cancer, ectopic pregnancy and pre-eclampsia, depression and postnatal depression, breast and ovarian cancer, lupus, and rheumatoid …
ACUTE RENAL INSUFFICIENCY FOLLOWING TRAUMA TO THE ABDOMINAL WALL
Authors: Maxwell L. Gelfand
Journal: JAMA (1953)

Acute renal insufficiency without nephritis has been more readily recognized in recent years. Although described by Minami1after World War I, it was not clearly understood until World War II, when a number of British investigators2drew attention to what they thought was a distinctive lesion observed in the kidneys of air raid casualties who came to autopsy after being buried under debris for several hours. They found that the glomeruli were almost completely intact and that the predominant lesion was confined to the lower nephrons. The lower nephrons showed focal degeneration and necrosis of the tubules, with heme casts in the lumens of these tubules. More recently, however, Oliver3and co-workers have clearly shown not that the lesion is restricted to any specific local area such as the lower nephrons, but that this destructive process may be irregular and may involve the proximal as well as
Inflammatory Bowel Diseases
Authors: Norton J. Greenberger
Journal: JAMA (1997)

The term inflammatory bowel disease (IBD) refers to a group of chronic inflammatory disorders of unknown cause involving the gastrointestinal tract. Although chronic IBD is usually divided into two groups, ie, ulcerative colitis and Crohn disease, it is recognized that approximately 10% to 15% of cases cannot be classified as either of these disorders, and such cases are termed "indeterminant colitis." The incidence and prevalence of these diseases vary considerably in different countries. For instance, the annual incidence of ulcerative colitis ranges from 3 to 15 per 100 000 with a prevalence of 70 to 150 per 100 000 in different countries. The annual incidence of Crohn disease ranges from 0.5 to 6 per 100 000 with prevalence of 20 to 75 per 100 000. If one were to extrapolate from these numbers it could be estimated that there are 375 000 cases of ulcerative colitis and 200 000 cases
Research bureaucracy in the United Kingdom: Research governance is about protection, not convenience
Authors: Justin T Denholm
Journal: BMJ (2004)

EDITOR—Jones and Bamford express surprise and frustration that their study was temporarily halted after they introduced an interview to the existing protocol without research ethics committee approval.1 They seem not to have recognised that introducing a new aspect to their project may bring additional ethical considerations and problems for their existing research aims.

They say that they did not …
Toward small animal models for the study of human hepatitis viruses
Authors: David G. Bowen
Journal: Hepatology (2010)

Abstract A paucity of versatile small animal models of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection has been an impediment to both furthering understanding of virus biology and testing antiviral therapies. We recently described a regulatable system for repopulating the liver of immunodeficient mice (specifically mice lacking fumaryl acetoacetate hydrolase [Fah], recombination activating gene 2 [Rag2], and the γ-chain of the receptor for IL-2 [Il-2rγ]) with human hepatocytes. Here we have shown that a high transplantation dose (3 × 106 to 5 × 106 human hepatocytes/mouse) generates a higher rate of liver chimerism than was previously obtained in these mice, up to 95% human hepatocyte chimerism. Mice with a high level of human liver chimerism propagated both HBV and HCV, and the HCV-infected mice were responsive to antiviral treatment. This human liver chimeric mouse model will expand the experimental possibilities for studying HBV and HCV infection, and possibly other human hepatotropic pathogens, and prove useful for antiviral drug testing.
Immunization of Babies with Diphtheria-Tetanus-Pertussis Prophylactic
Authors: M. Barr, A. T. Glenny, N. R. Butler
Journal: BMJ (1955)

<h3>Background</h3> Protein tyrosine phosphatases (PTPs) play critical roles in human autoimmunity. Previous studies found that PTPN2 may be the key regulatory factor in the T-cell-mediated immune response. PTPN2 regulates the Janus kinase/signal transducers and activators of transcription pathway by inhibiting signalling via the interleukin (IL)-2 receptor (CD122). An association between genetic variations in PTPN2 and CD122 with ocular Behcet’s disease (BD) has not yet been addressed and was therefore the purpose of this study. <h3>Methods</h3> A two-stage case–control study was performed in 906 patients with ocular BD and 2178 healthy controls. Genotyping analysis of 11 single nucleotide polymorphisms was carried out. The expression of PTPN2 in peripheral blood mononuclear cells (PBMCs) was quantified by real-time PCR and cytokine production was measured by ELISA. <h3>Results</h3> The frequency of the GG genotype of PTPN2-rs7234029 was significantly lower in patients with ocular BD (p=1.94×10<sup>−5</sup>, p<sub>c</sub>=8.34×10<sup>−4</sup>, OR=0.466). Stratification according to gender showed that rs7234029 was significantly associated with BD in men. A stratified analysis according to the main clinical features showed that rs7234029 was significantly associated with genital ulcers, skin lesions and a positive pathergy test. No association could be detected between BD and CD122 gene polymorphisms. Functional studies showed that rs7234029 GG genotype carriers had a higher PNPT2 mRNA expression level than those which carrying the AA or AG genotype, and a decreased secretion of IL-17 and tumour necrosis factor-alpha was seen by PBMCs from GG carriers. No significant difference could be detected concerning IL-1β or IL-6 production by stimulated PBMCs between the different genotype groups. <h3>Conclusions</h3> This study shows that a PTPN2-rs7234029 polymorphism is associated with ocular BD and is strongly influenced by gender. In addition, our results suggest that the genetic association with PTPN2 may involve the regulation of PTPN2 mRNA expression and cytokine secretion.
The effects of morphine on the mechanical properties of the systemic circulation in the dog.
Authors: J F Green, A P Jackman, G Parsons
Journal: Circulation Research (1978)

We studied the effects of morphine on the mechanical properties of the systemic circulation in nine mongrel dogs.A right heart bypass preparation allowed the separation of venous return into splanchnic and extrasplanchnic (peripheral) flows.Each channel was drained by gravity into an external reservoir.Blood then was pumped into the pulmonary artery at a constant but adjustable rate.Venous resistances and compliances of both channels were calculated from transient and steady state volume shifts which occurred after rapid drops in splanchnic and peripheral venous pressures.Arterial pressure and changes in reservoir volume were measured.The following data, (mean ± SE) were obtained with the pump flow set at 80 ml -min ' • kg" 1 .The administration of morphine did not produce a significant change from control splanchnic compliance (0.0177 ± 0.0023 liter/mm Hg), peripheral compliance (0.0259 ± 0.0017 liter/mm Hg), or peripheral venous resistance (5.6 ± 0.6 mm Hg-liter' 1 min).Morphine increased splanchnic venous resistance from 13.2 ± 1.4 to 20.6 ± 2.4 mm Hg liter" 1 min (P < 0.05); it decreased the percentage of cardiac output perfusing the splanchnic channel from 33 ± 2 to 24 ± 2 (P < 0.01) and increased the percentage perfusing the peripheral channel from 67 ± 2 to 76 ± 2 (P < 0.001).Arterial pressure fell from 92 ± 7 to 59 ± 5 mm Hg (P < 0.001).Splanchnic arterial resistance decreased from 140 ± 19 to 111 ± 17 mm Hg liter '• min (P < 0.01) and peripheral arterial resistance fell from 68 ± 8 to 36 ± 6 mm Hg • liter '• min (P < 0.001).Total peripheral resistance similarly declined from 51 ± 5 to 33 ± 4 mm Hg liter ' min (P < 0.001).Following the administration of morphine, the volume in the extracorporeal reservoir decreased by 0.508 ± 0.108 liter (P < 0.001).In four dogs before morphine and in all dogs after morphine, volume-flow relationships were determined by setting the pump to deliver five different flows (48, 64, 80, 96, and 112 ml -min' 1 -kg' 1 ) and observing the steady state change in reservoir volume.On the average, morphine shifted the volume-flow curve by 0.423 liter to the right along the volume axis (P < 0.02) and produced a slight statistically not significant increase in the slope.
Exercise training reduces sympathetic nerve activity in heart failure patients treated with carvedilol
Authors: Raffael Fraga, Fábio G. Franco, Fabiana Roveda, Luciana N.J. de Matos, Ana M.F.W. Braga, Maria U.P.B. Rondon, Daniel R. Rotta, Patricia C. Brum, Antonio C.P. Barretto, Holly R. Middlekauff, Carlos E. Negrão
Journal: European Journal of Heart Failure (2007)