tbuckley/cabot-search huggingface dataset:
Meeting Koch’s postulates for calcium signaling in cardiac hypertrophy
Authors: Kenneth R. Chien
Journal: Journal of Clinical Investigation (2000)

In 1890, a country doctor in Germany revolutionized our thinking of human disease. The challenge of the day was to identify specific bacterial agents that were responsible for major disease outbreaks. Robert Koch, after careful study of disease epidemics from around the world, forged the precepts that unequivocally establish causality for a single infectious agent in the onset of a distinct disease (1). These “postulates” stated that: (a) the agent should be present in every case of the disease; (b) the agent must be isolated from the diseased host and grown in vitro; (c) the disease must be reproduced when the agent is delivered to a susceptible host; and (d) the agent should be recovered from the diseased animals. Koch’s postulates formed the intellectual cornerstone for the next century of advances in microbiology and ultimately led to the discovery of the infectious basis for anthrax, cholera, and tuberculosis. In recognition of these seminal contributions, Robert A. Koch was awarded the 1905 Nobel Prize in Physiology and Medicine. As we enter a new century, it is becoming increasingly clear that the power of Koch’s logic has extended beyond the boundaries of bacterial diseases. Although his views were based on the inoculation of agents involved in infectious diseases, the clarity of his thinking continues to guide a new generation of scientists who are using germline transmission in the mouse to establish causality for specific genes and pathways in the etiology of complex, acquired human heart diseases. In this regard, the current article by Passier and colleagues is a valuable step toward fulfilling Koch’s postulates, underscoring the potential importance of calcium signaling pathways in cardiac hypertrophy and failure (2). Alterations in calcium handling have long been known to be closely associated with the onset of cardiac hypertrophy and failure. However, only recently has there been substantial evidence to support the notion that these changes in calcium might underlie pathways that contribute to the progression of either cardiac hypertrophy or failure. The discovery of calcium-calmodulin‐dependent protein kinases (3) and the subsequent identification of their critical role in neuronal cell signaling (4) laid the groundwork for a critical examination of the role of CaM kinase‐dependent signaling in in vitro cultured cardiac myocyte models of hypertrophy (5). By utilizing reporter genes that are activated during the hypertrophic response, it was subsequently shown that the δ isoform of CaM kinase II, which is translocated into the nucleus and is the predominant form of CaM kinase in the
Alteration of endothelium-dependent distribution of myocardial blood flow after coronary occlusion and reperfusion.
Authors: L R Pelc, J C Garancis, G J Gross, D C Warltier
Journal: Circulation (1990)

We have previously demonstrated that intracoronary infusion of the endothelium-dependent vasodilators acetylcholine, ATP, or arachidonic acid produces a preferential increase in subendocardial blood flow in anesthetized dogs. This study was performed to assess the effects of coronary artery occlusion and reperfusion on the distribution of myocardial blood flow produced by endothelium-dependent and endothelium-independent vasodilators. The endothelium was damaged by occlusion of the left anterior descending coronary artery for 45 minutes followed by 60 minutes of reperfusion in pentobarbital-anesthetized dogs. Intracoronary infusions of the endothelium-dependent vasodilators acetylcholine, bradykinin and thiazolylethylamine or the endothelium-independent vasodilator sodium nitroprusside were performed, and regional myocardial blood flow (by radioactive microspheres) was measured before and after occlusion and reperfusion. There were no changes in systemic hemodynamics during intracoronary infusion of vasodilators before or after coronary occlusion and reperfusion. All vasodilators produced similar increases in transmural blood flow before occlusion; however, only the endothelium-dependent vasodilators produced a significant increase in the subendocardial-to-subepicardial blood flow ratio. Increases in transmural flow as well as the preferential increase in subendocardial blood flow produced by acetylcholine, bradykinin, and thiazolylethylamine were attenuated after coronary occlusion and reperfusion. In contrast, increases in transmural blood flow produced by sodium nitroprusside were unchanged. These results suggest that the preferential increase in subendocardial perfusion produced by acetylcholine, bradykinin, and thiazolylethylamine is endothelium-dependent and may be selectively modified by ischemic insult.
Comparative risks of rhesus autoimmunisation in two different methods of mid-trimester abortion.
Authors: C Brewer, E W Ball, R Beard, P Gittins
Journal: BMJ (1981)

study showed a significant reduction in lower oesophageal sphincter pressure after intramuscular administration of emepronium bromide.In the nine patients who completed the study no significant change in sphincter pressure was found after four weeks' treatment with a standard oral dose of emepronium bromide.This may have been due to the much lower serum concentrations seen after oral medication than after intramuscular injection, confirming the findings of Ritch et al.5A local irritative effect of the tablets is probably the most common cause of oesophageal injury after oral medication, as no decrease in sphincter pressure was shown during oral treatment with emepronium bromide.Since, however, higher plasma concentrations of emepronium bromide decrease the sphincter pressure and the absorption of the drug from the gastrointestinal tract varies considerably, occasional high serum concentrations may be seen.This, combined with an individual variability in parasympathetic receptor sensitivity, might cause the lower oesophageal sphincter to relax, causing more severe cases of reflux oesophagitis in the lower oesophagus.
Abstract 2654: Transferrin receptor targeting PRINT® nanoparticles: Chemotherapeutic-free nanomedicine for B-cell lymphoma
Authors: Shaomin Tian, Jin Wang, Robby A. Petros, Mary E. Napier, Joseph M. DeSimone
Journal: Cancer Research (2010)

Abstract Transferrin receptor (TfR, CD71) is an essential protein involved in cellular iron uptake and regulation of cell growth. This study is to convert PRINT® nanoparticles to targeted drug delivery system by conjugating TfR ligands to particle surface, taking advantage of TfR overexpression on many types of malignant tissues. 200 nm × 200 nm cylindrical PRINT nanoparticles with poly(ethylene glycol)-based composition were fabricated and labeled with transferrin receptor antibody (mouse anti-human TfR mAb, clone OKT-9) or human transferrin (hTf) via biotin-avidin binding or direct chemical conjugation strategies. Nanoparticles coated with OKT9 or hTf, but not isotype control mouse IgG1 or bovine transferrin (bTf), showed highly specific TfR-mediated uptake by all human tumor cell lines tested in this study, including solid tumors and disseminating B cell lymphomas. Non-cancerous HEK293 cell that expresses low level of surface TfR, in contrast, took up particles at much lower rate during short exposure to TfR-targeting particles. The targeting efficiency was dependent on particle concentration, ligand density, particle dosing time and cell surface receptor level. Interestingly, the PRINT nanoparticles coated with OKT9 or hTf showed little cytotoxicity on all solid tumor cell lines tested but were toxic to Ramos B-cell lymphoma. More than 70% of the Ramos cells were killed by OKT9 or hTf coated nanoparticles at a concentration of 100 µg/mL. In contrast, free OKT9 or hTf did not induce death of Ramos cells. There was a strong correlation between TfR ligand density on particle surface and cell viability. Elevated caspase 3 activity indicates the activation of apoptosis pathways upon particle treatment. Iron supplementation suppressed toxicity of NP-OKT9 but not NP-hTf, suggesting different mechanisms by which hTf and OKT9 exerts cytotoxicity on Ramos cells. Further study of cell death mechanism through DNA microarray analysis is under way. Overall, we have shown that human transferrin and transferrin receptor antibodies can be useful targeting ligands for nanoparticle delivery to tumors. More importantly, non-toxic transferrin and TfR antibodies can be turned into a potential chemotherapeutic-free medicine for B-cell lymphoma through multiplexing with PRINT nanoparticles. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2654.
Extracellular Vesicles Modulate the Glioblastoma Microenvironment via a Tumor Suppression Signaling Network Directed by miR-1
Authors: Agnieszka Bronisz, Yan Wang, Michal O. Nowicki, Pierpaolo Peruzzi, Khairul I. Ansari, Daisuke Ogawa, Leonora Balaj, Gianluca De Rienzo, Marco Mineo, Ichiro Nakano, Michael C. Ostrowski, Fred Hochberg, Ralph Weissleder, Sean E. Lawler, E. Antonio Chiocca, Jakub Godlewski
Journal: Cancer Research (2013)

Abstract Extracellular vesicles have emerged as important mediators of intercellular communication in cancer, including by conveying tumor-promoting microRNAs between cells, but their regulation is poorly understood. In this study, we report the findings of a comparative microRNA profiling and functional analysis in human glioblastoma that identifies miR-1 as an orchestrator of extracellular vesicle function and glioblastoma growth and invasion. Ectopic expression of miR-1 in glioblastoma cells blocked in vivo growth, neovascularization, and invasiveness. These effects were associated with a role for miR-1 in intercellular communication in the microenvironment mediated by extracellular vesicles released by cancer stem–like glioblastoma cells. An extracellular vesicle–dependent phenotype defined by glioblastoma invasion, neurosphere growth, and endothelial tube formation was mitigated by loading miR-1 into glioblastoma-derived extracellular vesicles. Protein cargo in extracellular vesicles was characterized to learn how miR-1 directed extracellular vesicle function. The mRNA encoding Annexin A2 (ANXA2), one of the most abundant proteins in glioblastoma-derived extracellular vesicles, was found to be a direct target of miR-1 control. In addition, extracellular vesicle–derived miR-1 along with other ANXA2 extracellular vesicle networking partners targeted multiple pro-oncogenic signals in cells within the glioblastoma microenvironment. Together, our results showed how extracellular vesicle signaling promotes the malignant character of glioblastoma and how ectopic expression of miR-1 can mitigate this character, with possible implications for how to develop a unique miRNA-based therapy for glioblastoma management. Cancer Res; 74(3); 738–50. ©2013 AACR.
Keratinocyte class II histocompatibility antigen expression
Authors: B. J. Nickoloff, T. Y. Basham, T. C. Merigan, V. B. Morhenn
Journal: British Journal of Dermatology (1985)

Journal Article Keratinocyte class II histocompatibility antigen expression Get access B. J. Nickoloff, B. J. Nickoloff Department of Dermatology, Stanford Medical Center Stanford, CA 94305, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar T. Y. Basham, T. Y. Basham Department of Medicine, Stanford Medical Center Stanford, CA 94305, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar T. C. Merigan, T. C. Merigan Department of Medicine, Stanford Medical Center Stanford, CA 94305, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar V. B. Morhenn V. B. Morhenn Department of Dermatology, Stanford Medical Center Stanford, CA 94305, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 112, Issue 3, 1 March 1985, Pages 373–374, https://doi.org/10.1111/j.1365-2133.1985.tb04868.x Published: 01 March 1985
Characterisation of aorto-iliac arterial stenoses in terms of pressure and flow
Authors: A. R BAKER, D. R PRYTHERCH, D. H EVANS, P. R F BELL
Journal: Cardiovascular Research (1985)

Aorto-iliac stenoses were characterised in terms of pressure drop and flow velocity in a canine model and in patients with occlusive arterial disease. Pressure above and below the stenosis was measured intra-arterially and flow related measurements were made at rest and during reactive hyperaemia in the dog, and following papaverine administration in patients. The addition of flow velocity information to the pressure drop across a stenosis gave an increased separation of stenoses in the experimental animal and also in man.
Bromocriptine induced psychosis in acromegaly
Authors: I F Pye, R Abbott
Journal: BMJ (1983)

important match is unjustified when they are led to believe that the team is more important than the individual.These attitudes need urgent reappraisal.In May 1979 the Medical Officers of Schools Association issued a series of guidelines in an attempt to prevent or reduce the number of injuries.8In response the Rugby Football Union began collecting information about the number of neck injuries sustained in school matches with a view to publishing a definitive statement.6An accurate and definitive statement is long overdue on what has been a recognised problem for some time.The registration of all such injuries by schools and rugby clubs should be made com- pulsory and rigorously maintained by the Rugby Football Union or a similar responsible central body.This should include a description of the incident; the player's age, weight, and height; and, after consultation with an orthopaedic surgeon, details of the injury sustained.Meanwhile, the onus is on players to refrain from foul play and illegal tactics and on referees to be aware continually of the risks, to control the game, and to penalise the players appropriately.We hope that the spectacle of wheelchair bound, paraplegic, former rugby players being lined up to be greeted by their more fortunate colleagues will not be perpetuated.
Fluid Vaccin Virus.
Authors: W. V. Gage
Journal: JAMA (1899)

McCook, Neb., May 17, 1899. <h3>To the Editor:</h3> —At a meeting of the Nebraska State Medical Society, held May 9, I called attention to a new method of handling fluid vaccin virus. The method is simple, quick and efficacious, and will at once appeal to readers of the Journal: Break off both ends of the capillary tube of virus and blow the contents into a sterilizedspoon or other small receptacle. The one or two drops which go to make up the contents of the tube are then drawn into a sterile hypodermic needle, and the needle pushed just under the outer skin, where pressure on the piston of the hypodermic deposits the drop of serum. No dressing is necessary, for the skin furnishes a protection for the virus, and you will find that nearly all, if not all, of your cases thus inoculated will "take." The method takes less time
Electrical potential difference, sodium absorption and potassium secretion by the human rectum during carbenoxolone therapy.
Authors: A M Tomkins, C J Edmonds
Journal: Gut (1975)

The transmucosal electrical potential difference (pd) and the sodium and potassium net fluxes were measured in the rectum of subjects taking carbenoxolone. There was a rise in transmucosal pd persisting throughout treatment in all subjects which was accompanied by an increase in sodium absorption and potassium secretion. Comparison of the pd changes produced by carbenoxolone with those due to the mineralocorticoid 9-alpha-fluorocortisol showed that carbenoxolone had about 1/1000th the potency on a weight basis and the two drugs appeared to be additive in their effects. Topical instillation of carbenoxolone into the rectum produced an elevation of pd which persisted for three days. Amiloride and bendrofluazide did not interfere with these actions of carbenoxolone but spironolactone abolished them. One patient who developed fluid retention and hypokalaemia had a rectal pd similar to that of the other patients who had no side effects.
Loma Linda MD/Pilots Should Train at USC-Reply
Authors: W. Lawrence Beeson
Journal: JAMA (1991)

<h3>In Reply.</h3> —Since physicians, partly because of their economic status, are more likely than the general US population to own and use private aircraft,<sup>1,2</sup>their higher risk of death from aircraft accidents is not surprising (LLU, 38 deaths, standardized mortality ratio [SMR] = 1318; USC, 7 deaths, SMR = 360). As Dr Doram's letter underscores, what we could not account for in our study is why the risk of fatal aircraft accidents was three times higher for LLU physicians than for USC physicians (mortality ratio was 2.98 [95% confidence interval, 1.27 to 6.96]. We tested several hypotheses to elucidate this difference. <h3>The international service hypothesis.</h3> —Since LLU physicians provide service to the worldwide network of Seventh-day Adventist medical facilities, we tested the possibility that the increased risk of aircraft accidents might be attributed to the frequent use of private aircraft in their assignments. We found, however, that 88% of the aircraft
Atypical Lesions of the Anal Mucosa in Homosexual Men
Authors: Gerald Nash
Journal: JAMA (1986)

Recent studies suggest that there is an increased incidence of squamous cell carcinoma of the anus in male homosexuals, but a precursor lesion has not been identified. We retrospectively analyzed in a blind fashion all anal tissue removed surgically during 1984. Twelve (6.7%) of the 180 specimens from men contained lesions with foci of epithelial atypia. Only one (0.85%) of 118 specimens from women harbored similar atypia. Of seven additional file cases exhibiting atypical anal mucosa, six were from men. Of 14 men with atypical anal lesions whose sexual orientation was known, 11 (79%) were homosexuals. In the 20 cases found to have atypical mucosal lesions, three patterns of atypia were identified, with more than one often occurring in the same specimen. Anal intraepithelial neoplasia (dysplasia) was identified in seven cases (35%) and occurred primarily at the anorectal junction and in anal ducts. Atypical condyloma was found in three cases ( 15%). A third lesion histologically indistinguishable from Bowen's disease or bowenoid papulosis was found in 12 cases (60%). In ten of these the lesion was adjacent to a condyloma. Although the natural history of these lesions of the anal mucosa is presently unknown, it may resemble that of similar lesions in other anatomic locations. (<i>JAMA</i>1986;256:873-876)
Relationships between glucose metabolism and thermogenesis with and without prior exercise in obese women with non—insulin-dependent diabetes mellitus
Authors: Barry Braun, Michael B. Zimmermann, Norman Kretchmer
Journal: Metabolism (1996)

<h2>Abstract</h2> The rate of insulin-stimulated glucose disposal is reduced in individuals with insulin resistance, and is associated with a blunted or absent increase in energy expenditure in response to a glucose load. The magnitude of the effect of glucose on energy expenditure (EGEE) may be a function of opposing changes in the rate of glucose disposal (Rd) and hepatic glucose production (HGP). In this study, six women with non—insulin-dependent diabetes mellitus (NIDDM) were studied on a metabolic ward in each of three conditions. On days 1 and 2, they did no exercise (NX) or else performed low-intensity exercise ([LO]3,118 kJ [745 kcal]) at 50% maximal oxygen consumption [Vo<sub>2</sub>max]) or high-intensity exercise ([HI]3,114 kJ [744 kcal] at 75% Vo<sub>2</sub>max). On day 3, infusion of 6,6<sup>2</sup>H-glucose in the basal state was immediately followed by infusion of glucose, 6,6<sup>2</sup>H-glucose, and insulin at fixed rates. Indirect calorimetry was performed during the last 30 minutes of each infusion. EGEE was not different among the three conditions (mean ± SEM: NX −0.18 ± 0.11, LO −0.08 ± 0.05, and HI −0.08 ± 0.07 kJ/min) and was inversely related to steady-state plasma glucose concentration, a direct measure of insulin resistance (<i>r</i> = −.89, <i>P</i> < .05). EGEE was positively correlated with glucose Rd (<i>r</i> = .94, <i>P</i> < .001) and negatively correlated with HGP (<i>r</i> = −.91, <i>P</i> < .05). The data indicate that the glucose effect on energy expenditure was slightly positive in the more insulin-sensitive individuals, but negative in the more insulin-resistant subjects. The EGEE appears to be determined by the relative balance between energy required to store glucose and energy saved by suppression of glucose production.
The Antiquity and Origins of Rheumatoid Arthritis
Authors: Ronald E. Domen
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The report by Dequeker and Rico<sup>1</sup>describing rheumatoidlike lesions in a mid 15th- to early 16th-century painting, parallels a similar report by Appelboom et al.<sup>2</sup>At that time, evidence was also presented to support the paleopathological evidence for rheumatoid arthritis well before the 15th to 17th centuries.<sup>3</sup> American Indian skeletal material from Dickson Mounds, Ill, has yielded a case of rheumatoid arthritis in an elderly man from the Mississippian period (700 to 1650 AD).<sup>4</sup>Rothschild et al<sup>5</sup>have also published convincing evidence for the New World presence of rheumatoid arthritis during the Late Archaic Period (3000 to 5000 years before the present). Other cases have been reported.<sup>3</sup> To date, published reports support the possibility that rheumatoid arthritis originated in the New World and entered the Old World after the 15th century.<sup>5</sup>The paleopathological evidence supports the presence of rheumatoid arthritis
Failure of ACAT Inhibition to Retard Atherosclerosis
Authors: Sergio Fazio, MacRae Linton
Journal: New England Journal of Medicine (2006)

Medical management of atherosclerosis is based on the control of its risk factors (dyslipidemia, hypertension, family history, and smoking) and predisposing conditions (e.g., the metabolic syndrome and diabetes), but no drugs specifically target the arterial plaque. The search is on for therapeutic interventions that can act as antiatherosclerosis agents, selectively targeting one or more of the features of the atheroma, such as endothelial dysfunction, inflammation, or foam-cell formation.Approaches that target arterial plaque through the use of acyl–coenzyme A:cholesterol acyltransferase (ACAT) inhibitors have been investigated experimentally for two decades. ACAT inhibitors interfere with intracellular cholesterol transport within plaque macrophages and . . .