tbuckley/cabot-search huggingface dataset:
Transient elevations of cytosolic free calcium retard subsequent apoptosis in neutrophils in vitro.
Authors: M K Whyte, S J Hardwick, L C Meagher, J S Savill, C Haslett
Journal: Journal of Clinical Investigation (1993)

Elevation of cytosolic calcium ([Ca2+]i) has been reported to induce apoptosis in a number of cell types. However, in the neutrophil, which undergoes apoptosis constitutively during aging in vitro, activation by inflammatory mediators elevates [Ca2+]i and prolongs lifespan via inhibition of apoptosis. To examine this paradox, we investigated the effects of modulation of [Ca2+]i upon apoptosis of neutrophils in vitro. Calcium ionophores (A23187, ionomycin) retarded apoptosis in neutrophil populations after 20 h (P < 0.001). Conversely, intracellular Ca(2+)-chelation, using bis-(o-aminophenoxy)-N,N,N'N'-tetraacetic acid (BAPTA) acetoxymethyl ester (AM) promoted apoptosis (P < 0.02). W-7 (an inhibitor of calmodulin) also promoted apoptosis (P < 0.05). Measurements of [Ca2+]i, using fura-2, showed (a) increased apoptosis in neutrophil populations was not associated with elevated [Ca2+]i, (b) neutrophils cultured with ionophore at concentrations inhibiting apoptosis exhibited transient (< 1 h) elevations of [Ca2+]i, to levels previously reported with receptor-mediated stimuli, and (c) BAPTA was able to prevent the elevation of [Ca2+]i and the inhibition of apoptosis produced by ionophore. Modulation of apoptosis occurred without alterations in intracellular pH. Thus, in the neutrophil, unlike lymphoid cells, elevation of [Ca2+]i exerts an inhibitory effect upon apoptosis. Furthermore, these data suggest that transient elevation of [Ca2+]i elicits signaling events leading to prolonged inhibition of apoptosis.
Leflunomide Prevents Alveolar Fluid Clearance Inhibition by Respiratory Syncytial Virus
Authors: Ian C. Davis, Eduardo R. Lazarowski, Judy M. Hickman-Davis, James A. Fortenberry, Fu-Ping Chen, Xiaodong Zhao, Eric Sorscher, Lee M. Graves, Wayne M. Sullender, Sadis Matalon
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Previously, we demonstrated that intranasal infection of BALB/c mice with respiratory syncytial virus (RSV) resulted in an early 40% reduction in alveolar fluid clearance (AFC), an effect mediated via P2Y purinergic receptors.Objectives: To confirm that RSV-induced inhibition of AFC is mediated by uridine triphosphate (UTP), and to demonstrate that inhibition of de novo pyrimidine synthesis with leflunomide prevents increased UTP release after RSV infection, and thereby also prevents inhibition of AFC by RSV.Methods: BALB/c mice were infected intranasally with RSV strain A2. AFC was measured in anesthetized, ventilated mice by instillation of 5% bovine serum albumin into the dependent lung. Some mice were pretreated with leflunomide or 6-mercaptopurine.Measurements and Main Results: RSV-mediated inhibition of AFC is associated temporally with a 20-nM increase in UTP and ATP content of bronchoalveolar lavage fluid, hypoxemia, and altered nasal potential difference. RSV-mediated nucleotide release, AFC inhibition, and physiologic sequelae thereof can be prevented by pretreatment of mice with the de novo pyrimidine synthesis inhibitor leflunomide, which is not toxic to the mice, and which does not affect RSV replication in the lungs. In contrast, pretreatment of mice with 6-mercaptopurine, an inhibitor of de novo purine synthesis, has no beneficial effect on AFC or other indicators of disease progression. Finally, RSV-mediated inhibition of AFC is prevented by volume-regulated anion channel inhibitors.Conclusion: Pyrimidine synthesis or release pathways may provide novel therapeutic targets to counter the pathophysiologic sequelae of impaired AFC in RSV disease.
Endogenous Endothelin-1 Participates in the Maintenance of Cardiac Function in Rats With Congestive Heart Failure
Authors: Satoshi Sakai, Takashi Miyauchi, Takeshi Sakurai, Yoshitoshi Kasuya, Masaki Ihara, Iwao Yamaguchi, Katsutoshi Goto, Yasuro Sugishita
Journal: Circulation (1996)

Although it was demonstrated that circulating endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF), the production and roles of ET-1 in the failing heart are not known. We investigated the production of ET-1 in the heart and the density of myocardial ET receptors in rats with CHF. We also investigated the effects of intravenously infused BQ-123, an endothelin(A) (ETA) receptor antagonist, on both heart and myocardial contractility in rats with CHF.We used the left coronary artery-ligated rat model of CHF (CHF rats). Three weeks after surgery, the rats developed CHF. Plasma ET-1 concentration was significantly higher in the CHF rats than in the sham-operated rats (P<.01). In the left ventricle, the expression prepro-ET-1 mRNA was markedly higher in the CHF rats than in the sham-operated rats. The peptide level of ET-1 in the left ventricle was also significantly higher in the CHF rats than in the sham-operated rats (500+/-41 versus 102+/-10 pg/g tissue, P<.01). Myocardial ET receptors were significantly higher in the CHF rats than in the sham-operated rats (243+/-20 versus 155+/-17 fmol/mg protein, P<.05). In the CHF rats, intravenous BQ-123 infusion (0.1 mg x kg(-1) x min(-1) for 120 minutes) significantly decreased both heart rate (P<.01) and LV+dP x dt(max) (P<.05) but not mean blood pressure. BQ-123 infusion did not affect these hemodynamic parameters in the sham-operated rats.In the present study, we demonstrated that the production of ET-1 in the heart is markedly increased and that the density of myocardial ET receptors is significantly elevated in the CHF rats. Intravenous BQ-123 infusion significantly reduced both heart rate and LV+dP/dt(max) in the CHF rats but not in the sham-operated rats. Therefore, the ET receptor-mediated signal transduction system in the heart appears to be markedly stimulated in the CHF rats, and endogenous ET-1 may be involved in the maintenance of the cardiac function in these rats.
AN ELECTRON MICROSCOPE STUDY OF THE GLOMERULUS IN NEPHROSIS, GLOMERULONEPHRITIS, AND LUPUS ERYTHEMATOSUS
Authors: Marilyn G. Farquhar, Robert L. Vernier, Robert A. Good
Journal: The Journal of Experimental Medicine (1957)

Renal biopsies from 16 patients with nephrosis, 7 patients with glomerulonephritis, and 3 patients with disseminated lupus erythematosus were studied with the electron microscope. The observations presented indicate that early in the course of each of these diseases alterations occur in the fine structure of the glomeruli which serve to distinguish one disease process from another. In nephrosis, some distortion of the organization of the epithelial foot processes was seen in all patients. These epithelial changes constituted the early, consistent lesion of the disease. There was frequently also a swelling of the endothelium. In glomerulonephritis, pronounced proliferative changes involving the endothelium and to a lesser extent the epithelium, together with the laying down of a basement membrane-like material, represented the predominate pathologic processes. There was also a swelling of both endothelial and epithelial cytoplasm. The epithelial foot processes generally appeared normal. In patients with a clinically "mixed" picture of nephrosis and nephritis, the glomerular changes were likewise "mixed," for various combinations of epithelial, endothelial, and basement membrane abnormalities were present. In disseminated lupus erythematosus, a more or less generalized thickening of the basement membrane proper associated with a variable degree of endothelial proliferation was seen. It is suggested that an accentuation of the process of basement membrane thickening results in the "wire loop" appearance sometimes seen by light microscopy. Although the earliest alterations in glomerular fine structure were characteristic for each of the disease processes, at later stages the changes were not always distinctive. The resulting scarred or "hyalinized" glomeruli, composed of relatively homogeneous, basement membrane-like material, and a few atrophic cells, appeared quite similar. Although the functional implications of the structural changes observed remain obscure at this time, it is believed that insight into mechanisms may stem from such observations.
Abstract 5055: Efficacy of cabazitaxel in mouse models of pediatric brain tumors.
Authors: James M. Olson, Emily Girard, Sally Ditzler, Andrew Richards, Doonhoon Lee, Patricia Vrignaud
Journal: Cancer Research (2013)

Abstract Successful treatment of pediatric brain tumors is limited by significant long-term toxicities associated with surgery and radiation therapy on the developing central nervous system There is an unmet need for chemotherapy with improved efficacy in difficult to treat tumors, such as supratentorial primitive neuroectodermal tumors (sPNET) and atypical teratoid/rhabdoid tumors (ATRT), as well as diagnoses that currently have good long-term survival, such as medulloblastoma. Overcoming the blood brain barrier is a large hurdle in effectively treating brain tumors, particularly when there is a need, as with very young patients, to avoid radiation therapy. Cabazitaxel is a promising taxane derivative shown to effectively kill tumor cells in pre-clinical in vitro and in vivo experiments. Similar to docetaxel, cabazitaxel has favorable drug properties and a manageable safety profile in patients with advanced solid tumors, with the advantage of being able to cross the blood brain barrier. Additionally, cabazitaxel has shown efficacy in docetaxel resistant tumors. The experiments presented here, tested the relative efficacy of cabazitaxel and docetaxel in mouse models of pediatric brain tumors. A spontaneous mouse model of medulloblastoma driven by Smo activation was evaluated by magnetic resonance imaging for tumor growth and blood brain barrier integrity before and after treatment with cabazitaxel or docetaxel. Efficacy of cabazitaxel and docetaxel against patient-derived pediatric brain tumors was tested in flank and orthotopic xenograft models of medulloblastoma, sPNET, ATRT, and ependymoma. We observed regression in some flank xenograft tumors after treatment with cabazitaxel or docetaxel, with evidence of superior action of cabazitaxel. These data support further testing of cabazitaxel as a therapy to treat human pediatric brain tumors. This work has been funded by Sanofi Inc. Citation Format: James M. Olson, Emily Girard, Sally Ditzler, Andrew Richards, Doonhoon Lee, Patricia Vrignaud. Efficacy of cabazitaxel in mouse models of pediatric brain tumors. [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 5055. doi:10.1158/1538-7445.AM2013-5055
Inhibition of the transport of HIV in vitro using a pH-responsive synthetic mucin-like polymer system
Authors: Alamelu Mahalingam, Julie I. Jay, Kristofer Langheinrich, Shetha Shukair, Mike D. McRaven, Lisa C. Rohan, Betsy C. Herold, Thomas J. Hope, Patrick F. Kiser
Journal: Biomaterials (2011)
Evaluation of Persons Exposed to Dairy Products Contaminated With Heptachlor
Authors: Paul A. Stehr-Green
Journal: JAMA (1986)

To the Editor.—  Heptachlor, a chlorinated cyclodiene pesticide, was registered in 1952 as a commercial pesticide for foliar, soil, and structural applications. After 1960, it was used primarily in soil applications against agricultural pests and termites. 1 As a result of positive findings in carcinogenicity assays, the Environmental Protection Agency suspended all uses of products containing heptachlor in 1976, except for treatment of seeds, control of ants on Hawaiian pineapple plants, and control of termites and the narcissus bulb fly. 2   In January 1986, heptachlor and related pesticide residues (eg, chlordane) were found at a concentration of approximately 10 ppm in both grain and mash being sold for cattle feed by a gasohol production plant in Van Buren, Ark. In early March 1986, testing of raw milk from more than 1200 dairy farms resulted in the placing in quarantine of 33 farms in Arkansas and five others in Missouri and
WHO workers are shot at during vaccination campaign in Pakistan
Authors: A. Gulland
Journal: BMJ (2012)

The World Health Organization has insisted that the polio vaccination campaign in Pakistan will continue despite an armed attack on two workers on 17 July.

The two men, a WHO staff member and an international consultant, were in a stable condition after their vehicle was shot at in the city of Karachi. A WHO statement said there was “no evidence to suggest that this was a deliberate or targeted attack against polio eradication efforts or WHO.”

The statement continued: “This incident will not distract from the progress Pakistan is making this year, as the country is closer than ever to eradication.”

The incident happened during the country’s National Immunisation Days, between 16 and 18 July, …
New approaches for detecting and curtailing foodborne microbial infections
Authors: J. Stephenson
Journal: JAMA (1997)

ABSTRACT HEADLINES of recent foodborne disease outbreaks—strawberries tainted with hepatitis A virus, unpasteurized apple juice contaminated with Escherichia coli 0157:H7, raspberries harboring Cyclospora cayetanensis—are doing much to fuel the perception that microbial pathogens are gaining an upper hand. But while it's true that such pathogens are evolving new tricks and exploiting new opportunities, epidemiologists and laboratory scientists are countering with new strategies that promise to revolutionize the detection of infections caused by foodborne microbes.See also pp 1340 and 1344National surveillance of foodborne diseases at a group of sentinel public laboratories around the nation, sophisticated technologies such as DNA fingerprinting to pinpoint specific bacterial subtypes responsible for an outbreak, and computer networks that link and analyze the findings of far-flung laboratories may soon provide public health experts with an early warning system far beyond what is possible today.Although such efforts have been in progress during the past
Improvements in the treatmant of elderly patients with unstable angina results from the GUARANTEE registry
Authors: M.T. Roe, D.J. Moliterno, C.P. Cannon, N.R. Every, F.V. Aquino, C.B. Granger, S. Sapp, J. Booth, J.J. Ferguson
Journal: Journal of the American College of Cardiology (1998)
Cardiac morphology at late fetal stages in the mouse with trisomy 16: consequences for different formation of the atrioventricular junction when compared to humans with trisomy 21
Authors: S Webb
Journal: Cardiovascular Research (1997)

Objective: The mouse with trisomy 16 (Ts16) is held to be a genetic model for humans with Down's syndrome (Ts21). Both trisomies are associated with atrioventricular septal defects, but the precise morphology in the mouse remains unclear. We have therefore characterised cardiac morphology in the mouse with Ts16. Methods: Ts16 fetuses, from a Rb(11.16)2H/Rb(16.17)7Bnr×C57BL/6J cross, were collected on gestational days 17 or 18 (full term = 19 days) and studied using scanning electron microscopy and serial sections. Results: The hearts showed a spectrum of deficient atrioventricular septation which we categorised into two types. In one, a common atrioventricular junction was separated into right and left orifices by a tongue of tissue joining two valvar leaflets that bridged the ventricular septum to varying extent. In the other, a common atrioventricular junction was connected exclusively to the left ventricle. All hearts had ostium primum atrial and ventricular septal defects, together with abnormal ventriculo-arterial connections. No heart had the typical morphology seen in the human with Down's syndrome, namely a balanced common atrioventricular junction, guarded by a common valve, with the aorta connected exclusively to the left ventricle. Conclusions: The cardiac defects seen in Ts16 mice show marked differences from the typical anatomy in human Ts21, suggesting more complex mechanisms of cardiac dysmorphogenesis in Ts16. The mouse model will prove valuable in elucidating the mechanism of normal expansion of the atrioventricular junctions, and help in charting the precise steps involved in atrial and ventricular septation.
A Disorder of Muscle Lipid Metabolism and Myoglobinuria
Authors: William J. Bank, Salvatore DiMauro, Eduardo Bonilla, David M. Capuzzi, Lewis P. Rowland
Journal: New England Journal of Medicine (1975)

Two brothers, 29 and 33 years of age, had recurrent myoglobinuria, renal failure and azotemia, but were otherwise normal, without apparent muscle weakness or exercise intolerance. Ischemic exercise resulted in normal lactate production. Muscle glycogen content and activities of phosphorylase and phosphofructokinase were normal. Plasma triglycerides were elevated (500 mg per deciliter) on a regular diet and rose during fasting. During a 72-hour fast, serum creatine phosphokinase rose more than 10 times, and myoglobin was detected in urine. Plasma ketone production was minimal during fasting, but prompt ketonemia (a normal response) occurred after ingestion of medium-chain triglycerides. Carnitine palmityl transferase activity was virtually absent in crude muscle extracts and mitochondrial fractions. Lack of this enzyme impairs long-chain fatty acid utilization, reflected in increased content of plasma free fatty acids and plasma triglycerides. Depletion of ATP because of this metabolic block in muscle may account for the attacks of myoglobinuria. (N Engl J Med 292:443–449, 1975)
Diabetic renal disease: differences between Asian and white patients
Authors: J K Cruickshank
Journal: BMJ (1986)

pattern of mental handicap, with an explanation about the as yet himted predictive value of these.The problems with predictive testing are a fturther example of the ethical difficulties which beset research workers.It is becoming increasingly obvious that the division between clinical and research work is not clear and that the guidelines for the research worker's responsibility to his clients need better definition.
Gastric Wall Invasion Following Transjugular Intrahepatic Portosystemic Stent Shunt Insertion for Variceal Bleeding
Authors: D. Tripathi, J. Plevris, D. Redhead, P. Hayes
Journal: Endoscopy (2006)

Transjugular intrahepatic portosystemic stent shunt (TIPSS) insertion has been extensively used in the management of the complications of portal hypertension for over 10 years [1]. We report two unusual cases, brought to light during routine endoscopy, that illustrate technical complications of TIPSS not previously reported.
Are medical secrets up for grabs?
Authors: Rebecca Coombes
Journal: BMJ (2007)

The NHS's ill fated computer project has made the news again, this time over the government's climbdown from putting medical records on a national database. 

With public confidence in the ongoing £20bn upgrade of NHS computer systems right down there with the government's handling of Iraq, the news that electronic medical records would not, as originally planned, be automatically uploaded to a central computer “spine” was mothers' milk to British newspapers. 

The security of the sinister sounding “spine” was the main focus of press concern. Do people want to risk others finding out they were a teenage bed wetter, or once had anal warts? 

Under the initial proposals, summary patient records—including medicines taken, adverse reactions, and allergies—were to be made available for access nationally by GPs and hospitals. Under pressure, health minister Lord Warner produced a report the week before Christmas, promising patients an opt out. This softened approach would also allow patients to access and amend online records before they are sent to the national database. 

The Guardian , which had been running a campaign against a compulsory national database of …
Effect of iron complexes on adjuvant arthritis in rats.
Authors: A J Dabbagh, D R Blake, C J Morris
Journal: Annals of the Rheumatic Diseases (1992)

When a total dose infusion of iron dextran is given to anaemic rheumatoid patients an exacerbation of inflammatory synovitis in previously affected joints is observed. The adjuvant arthritis model of inflammation in rats has been used to investigate the mechanism of iron promoted synovitis. Either iron dextran (5 mg injected intravenously) with a dextran C control, or iron sorbitol (7.5 mg injected intramuscularly) with a sorbitol citrate complex control was given at the onset of clinical joint inflammation. Iron dextran significantly increased joint inflammation (assessed by joint scoring) at days 12, 13, 14, and 16 after injection. Similarly, iron sorbitol produced a significant increase in the joint score at days 17, 18, 19, and 21. In addition, extensive osteoporosis was observed in the rats treated with iron sorbitol. These pro-inflammatory effects of iron coincide with the presence of positive results for synovial iron (III) using Perl9s test and neutrophil infiltration. The results of this study suggest that the iron induced increase in synovitis in adjuvant arthritis is a result of iron promoted oxidative damage and is not likely to be due to the dextran C or the sorbitol citric acid components. It is suggested that a similar mechanism may occur in rheumatoid patients given iron supplements.
Patient Mix and Utilization of Resources
Authors: Daniel Z. Louis
Journal: JAMA (1993)

<h3>To the Editor.</h3> —Two recent articles described results from the Medical Outcomes Study.<sup>1,2</sup>Significant differences were reported in the mix of patients among medical specialties and in resource utilization among specialties controlling for patient mix. We are troubled by problems in the diagnostic accuracy, lack of specificity, and the authors' use of the measures of clinical severity for patients with hypertension, diabetes mellitus, recent myocardial infarction, and congestive heart failure. It appears that patients were assigned diagnostic labels based on physician reports. Was any attempt made to validate the accuracy of the diagnosis? Were any laboratory data collected that document that the patient had the diagnosis assigned by the physician? Is it possible that some physicians were more accurate in their diagnoses than others? The instruments used to measure disease severity lack specificity. The cause is not stated for either congestive heart failure or hypertension although cause is important