tbuckley/cabot-search huggingface dataset:
Effects of synthetic atrial natriuretic peptide on renal function and renin release in acute experimental heart failure.
Authors: T A Scriven, J C Burnett
Journal: Circulation (1985)

Studies were performed in anesthetized control dogs (n = 6) and in dogs (n = 6) with acute low-output heart failure produced by inflation of a balloon in the thoracic inferior vena cava. Studies were designed to determine the effects of synthetic atrial natriuretic peptide on renal function and renin release in this acute high-renin, sodium-retaining preparation. Intrarenal infusion of synthetic atrial natriuretic peptide (0.3 micrograms X kg-1 X min-1) resulted in decreases in arterial pressure and renal blood flow in both groups. Glomerular filtration rate increased in both low-output (delta + 10.7 +/- 3.1 ml/min) and control (delta + 8.7 +/- 2.9 ml/min) groups. Fractional lithium excretion, a marker of proximal tubule reabsorption, also increased in both low-output (delta + 12.0 +/- 4.6%) and control (delta + 14.3 +/- 5.0%) groups. Renin secretory rate decreased in the low-output group from 852.8 +/- 183.0 to 149.5 +/- 73.7 ng/min and in the control group from 308.5 +/- 84.5 to 44.5 +/- 27.5 ng/ml. Intrarenal infusion of atrial natriuretic peptide resulted in an attenuated increase in both urinary sodium excretion (delta + 42.3 +/- 10.7 vs delta + 201.2 +/- 37.9 mueq/min) and fractional excretion of sodium (delta + 0.48 +/- 0.13% vs delta + 2.85 +/- 0.45%) in the low-output as compared with the control group. Our studies demonstrate that administration of synthetic atrial natriuretic peptide results in an increase in glomerular filtration rate and a decrease in proximal tubule reabsorption, as estimated by lithium excretion, in both control dogs and those with acute low-output heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
Primary autoimmune diabetes mellitus.
Authors: R S Gray, B F Clarke
Journal: BMJ (1978)

Britain this solution is called Synthamin.Recently minor elevations of serum bilirubin concentration and major elevations of serum alkaline phosphatase and aspartate amino- transferase activities have been observed in six patients receiving this solution following surgery of the head and neck.These patients did not have evidence of metastatic disease and no abnormalities have been observed in patients undergoing similar operations who did not receive nutritional support.However, the same type of biochemnical abnormalities have been seen in a patient receiving the intravenous amino-acid solution Vamin.Furthermore, 15 patients who received a nasogastric diet based on the beef protein derivatives Albumaid or Serameen and the glucose polymer Caloreen showed the same biochemical response.This latter observation would suggest that cholestasis occurring in patients receiving intravenous nutrients is unlikely to be due to a lack of stimulation of bile flow by food in the gut.Are these changes due to the absence of some dietary component or presence of some chemical agent that is common to artificial diets whether given intravenously or by the nasogastric route ?These results will be reported in detail elsewhere.
Abstract 279: A small molecular miR-21 inhibitor inhibits glioma cell invasion and mesenchymal transition via upregulation of VHL expression.
Authors: Zhendong Shi, Junxia Zhang, Lei Han, Kailiang Zhang, Luyue Chen, Xiaomin Qian, Peiyu Pu, Chunsheng Kang
Journal: Cancer Research (2013)

Abstract Glioblastomas (GBMs) are the most common malignant brain tumors which characterized by rapid and invasive growth. Accumulating evidence points to a critical role of EMT like events during glioma progression and malignant transformation. Cancer cells undergoing EMT can acquire invasive properties and enter the surrounding stroma, resulting in the creation of a favorable microenvironment for cancer progression and metastasis. In this study, we identified a small molecular miR-21 inhibitor through a high-throught screening approach and found it significantly repressed the U87 and LN229 glioma cell migration and invasion. Meanwhile, VHL, a direct target of miR-21, was increased expression in mRNA and protein level after this miR-21 inhibitor treatment, but the β-catenin expression was reduced. Silencing of VHL using small interefering RNA (siRNA) also reduced β-catenin expression. Furthermore, suppression of β-catenin transactivation by miR-21 inhibitor, through upregulation of VHL expression, increased E-cadherin expression and partially reversed the epithelial-mesenchymal transition (EMT). On the other hand, confocal microscopy and Western blot assay presented that N-cadherin, ZEB1, ZEB2 and MMP9 expression were reduced. Additionally, in a U87 intracranial glioma xenograft nude mice model, we found a less invading tumor edge of miR-21 inhibitor treated group in comparison with DMSO group. Moreover, there was an increased expression of E-cadherin and reduced expression of β-catenin, N-cadherin, ZEB1, ZEB2 and MMP9 in tumor samples after the inhibitor treatment. Together, these results provided insight into the specific treatment efficacy of this small molecular inhibitor in EMT and tumor metastasis, which achieved via up-regulation of VHL expression. Therefore, it might be a novel and potentially antimetastatic agent for therapeutic intervention in glioblastomas in future. Citation Format: Zhendong Shi, Junxia Zhang, Lei Han, Kailiang Zhang, Luyue Chen, Xiaomin Qian, Peiyu Pu, Chunsheng Kang. A small molecular miR-21 inhibitor inhibits glioma cell invasion and mesenchymal transition via upregulation of VHL expression. [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 279. doi:10.1158/1538-7445.AM2013-279
Evidence of net benefit of proton pump inhibitors with clopidogrel is lacking in older patients
Authors: M. D. Witham, R. Soiza, I. Logan
Journal: BMJ (2012)

Although proton pump inhibitor (PPI) use was not associated with increased risk of myocardial infarction in people on dual antiplatelet treatment,1 we are worried by the linked editorial’s suggestion that PPIs should therefore be prescribed to a wide range of patients on this treatment.2

PPIs have …
Bladder Sphincter Verge Urethral Pressure Reduces Pain Scores in Men Undergoing First Ever Flexible Cystoscopy
Authors: Sashi S. Kommu, Zafar Hashim, David Cartlidge, Thomas Finnigan, Anurag Golash, Christopher J. Luscombe, Samson Liu, Mark F. Saxby, Jerry B. Emtage
Journal: International Journal of Surgery (2010)
Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells.
Authors: R J North
Journal: The Journal of Experimental Medicine (1982)

On the basis of preceding studies showing that tumor-induced, T cell-mediated immunosuppression serves as an obstacle to adoptive immunotherapy of the Meth A fibrosarcoma, it was predicted that cyclophosphamide treatment of tumor bearers would remove this obstacle and allow passively transferred immune T cells to cause tumor regression. It was found that infusion of immune spleen cells alone had no effect on tumor growth, and cyclophosphamide alone caused a temporary halt in tumor progression. In contrast, combination therapy consisting of intravenous injection of 100 mg/kg of cyclophosphamide followed 1 h later by intravenous infusion of tumor-immune spleen cells caused small, as well as large tumors, to completely and permanently regress. Tumor regression caused by combination therapy was completely inhibited by intravenous infusion of splenic T cells from donors with established tumors, but not by spleen cells from normal donors. These suppressor T cells were eliminated from the spleen by treating the tumor-bearing donors with 100 mg/kg of cyclophosphamide. Immune T cells, in contrast, were resistant to this dose of cyclophosphamide. These results show that failure of intravenously-infused, tumor-sensitized T cells to cause regression of the Meth A fibrosarcoma growing in its syngeneic or semi-syngeneic host is caused by the presence of a tumor-induced population of cyclophosphamide-sensitive suppressor T cells.
Incentivizing “Structures” Over “Outcomes” to Bridge the Knowing-Doing Gap
Authors: Craig A. Umscheid, Patrick J. Brennan
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Abstract S5-4: Synthetic-Lethality of Triple-Negative Breast Cancers Via the MYC Oncogene Pathway
Authors: A Goga, D Horiuchi, L Kusdra, S Chandriani, ME Lenburg, AM Gonzalez-Angulo, NE Huskey, KJ Creasman, SE Davis, GB Mills, LJ. Esserman
Journal: Cancer Research (2010)

Abstract Background: Breast cancer lacking the estrogen, progesterone and ERBB2 receptors, (“triple-negative”) encompasses an aggressive sub-type that is associated with a higher incidence of early tumor recurrence and poor patient outcome, particularly after distant relapse. The lack of validated targets means that only conventional cytotoxic chemotherapy offers significant benefits, albeit with associated toxicities and lack of specificity. Among many potential therapeutic targets in triple-negative breast cancer, MYC may be important as its function is elevated in many breast cancers with aggressive phenotypes. Methods: In this study we investigate the association between MYC abundance in primary breast tumors using two large clinical cohorts and examined MYC mRNA and protein abundance as well as the expression of a MYC gene signature. We next examined the association between the MYC gene signature and patient response to neoadjuvant chemotherapy as well as disease-free survival in the ISPY TRIAL. Furthermore, we examined whether high MYC expression in triple-negative tumors might provide a new therapeutic approach in this tumor sub-type. We tested a synthetic-lethal strategy to kill triple-negative breast cells with abundant MYC expression by inhibiting cyclin-dependent kinases (CDKs). Results: We find that human triple-negative breast cell lines have significantly elevated MYC mRNA and protein expression. These results were validated using primary patient tumor samples from the neoadjuvant ISPY TRIAL (N= 138 patients) as well as a separate cohort of primary tumor samples for which quantitative protein expression was determined (N= 208 patients). In the ISPY TRIAL an increased expression of the MYC gene signature was associated with worse outcome in patients with substantial residual tumor burden after neoadjuvant chemotherapy (RCB Class II and III). We sought to exploit this increased MYC activity in triple-negative tumors using a synthetic-lethal approach dependent on cyclin-dependent kinase (CDK) inhibition. We found that triple-negative breast tumor cells undergo cell death in a MYC-dependent manner following treatment with several CDK inhibitors, including SCH72796 that is in Phase II clinical trials. We find that CDK inhibition effectively induces tumor regression in human tumor xenografts. CDK inhibition in triple-negative breast cells up-regulates the pro-apoptotic BCL2 family member BIM. Our findings support the exploration of CDK inhibitors as treatment for triple-negative breast cancers. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S5-4.
Exercise Radionuclide Ventriculography in Patients with Strongly Positive Electrocardiograms and Normal Reperfusion Thallium Studies
Authors: Aaron Kenigsberg, Stanley Lewis, Thomas Hill, O Stevens Leland, Eliot Young
Journal: Clinical Nuclear Medicine (1989)

Kenigsberg, Aaron; Lewis, Stanley; Hill, Thomas; Leland, O. Stevens; Young, Eliot Author Information
Abstract B28: Downregulation of vimentin confers resistance to the microtubule stabilizing agents peloruside A and laulimalide in 1A9 human ovarian carcinoma cells
Authors: Arun Kanakkanthara, Pisana Rawson, Peter T. Northcote, John H. Miller
Journal: Clinical Cancer Research (2012)

Abstract Microtubule-targeting agents are an important class of drugs for the treatment of cancer. Although the development of drug resistance in cancer cells often limits the clinical efficacy of these agents, the mechanisms of resistance are not fully understood. Peloruside A (PLA) and laulimalide (LAU) are two marine sponge-derived stabilizing agents of microtubules. PLA and LAU represent the only known class of non-taxane site binding microtubule stabilizing agents and have a number of clinically useful potential advantages over paclitaxel, a widely used tubulin-targeting anticancer drug, including reduced susceptibility to the multidrug resistance P-glycoprotein efflux pump, good efficacy against taxane-resistant cells with mutations in the taxoid site, and more effective antitumor effects in non-small cell lung tumor xenografts. To understand the mechanisms of resistance to PLA and LAU, we used two drug-resistant sublines of the 1A9 human ovarian carcinoma cell line, R1 and L4. R1 cells are 6-fold resistant to PLA but remain fully sensitive to LAU; whereas, the L4 cells are 39-fold resistant to both PLA and LAU. We previously showed that both resistant cell lines exhibit different single point-mutations in their βI-tubulin gene. The L4 cells also have a high abundance of βII- and βIII-tubulin isotypes, which play a partial role in the resistance phenotype. To determine other protein changes that might contribute to the resistant phenotype of the R1 and L4 cells, we examined the proteome of the resistant cells using two-dimensional differential in-gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The proteomic analysis identified several proteins that were significantly altered relative to the parental 1A9 cells, including a decreased expression of vimentin in L4 cells. Using Western blotting and immunocytochemistry, the decrease in vimentin abundance seen in 2D-DIGE was confirmed. Vimentin levels were unchanged in the PLA-resistant R1 cells as well as two paclitaxel/epothilone-resistant sublines of 1A9 cells. Transfection with a full-length human vimentin cDNA partially restored sensitivity of L4 cells to PLA and LAU by 23% and 17% respectively. In vimentin-expressing parental 1A9 cells, tubulin-targeting and DNA-damaging agents caused degradation of vimentin and generation of vimentin degradation products. In conclusion, this study is the first to demonstrate a novel function for vimentin as a cellular determinant of the response to microtubule stabilizing agents, and that this effect is likely to be associated with the mode of cell killing by these agents. Since many of the proteins identified in this study have not previously been shown to play a role in drug resistance, our results also introduce potential new mechanisms by which cancer cells may become resistant to antimicrotubule agents.
Synthesis of Luminescent Near-Infrared AgInS<sub>2</sub> Nanocrystals as Optical Probes for In Vivo Applications
Authors: Liwei Liu, Rui Hu, Indrajit Roy, Guimiao Lin, Ling Ye, Jessica L. Reynolds, Jianwei Liu, Jing Liu, Stanley A. Schwartz, Xihe Zhang, Ken-Tye Yong
Journal: Theranostics (2013)

Near infrared quantum dots have been receiving great attention as fluorescent optical probes for in vivo imaging applications. In this contribution, we report the synthesis and surface functionalization of cadmium free ternary AgInS2 nanocrystals emitting in the near infrared range for successful in vitro and in vivo bioimaging applications. The FDA approved triblock copolymer Pluronic F127 was used to encapsulate the nanocrystals and made them dispersible in aqueous solution. By employing a whole body small animal optical imaging setup, we were able to use the AgInS2 nanocrystals formulation for passive targeted delivery to the tumor site. The ultra-small crystal size, near-infrared emitting luminescence, and high quantum yield make the AgInS2 nanocrystals an attractive candidate as a biological contrast agent for cancer sensing and imaging.
"Sniffing" and addiction.
Authors: J. Todd
Journal: BMJ (1968)

sions when toxic buccal and gastrointestinal symptoms develop to mild or moderate severity.One patient received an initial infusion of 11 g. in five days without any clinical benefit or toxic symptoms.Six weeks later infusion was repeated.A total of 31 g. was administered in 14 days.This was excessive, causing severe gastrointestinal and haernatological effects, but recovery was rapid.The most recent case, a young British migrant, received 19 g. in nine days into the hepatic artery (not the coeliac axis).This infusion was deliberately terminated early because the patient intended to, and three weeks later did, return to Britain, with a patent catheter
STUDIES ON EXPERIMENTAL PNEUMONIA
Authors: Francis G. Blake, Rusell L. Cecil
Journal: The Journal of Experimental Medicine (1920)

Study of the pathology of pneumonia experimentally produced in monkeys by the intratracheal injection of pneumococcus has shown that it is identical with the pathology of lobar pneumonia in man. It has been found that the pneumococcus primarily invades the pulmonary tissue at some point or points in the portion of the lobe proximal to the hilum, that it spreads rapidly throughout the lobe by way of the perivascular, peribronchial, and septal interstitial tissue and lymphatics, quickly reaching the pleura, and that it invades the alveolar structure primarily by way of the alveolar walls, subsequently passing into the alveolar spaces simultaneously with the outpouring of exudate into the alveoli. It has been shown that the initial mode of invasion may be by direct penetration at one or more points into the walls of the larger bronchi near the hilum. The possibility that primary invasion may occur in terminal bronchioles, alveolar ducts, or alveoli of the parenchyma near the hilum has not been certainly excluded, though the evidence is against this supposition. In harmony with the mode of distribution of pneurnococci it has been found that the initial lesions of lobar pneumonia are of the interstitial framework of the lung, with respect both to the grosser framework and to the alveolar framework. Hepatization begins centrally and spreads toward the periphery and is a constantly progressive process. With the development of hepatization the conspicuous interstitial lesions of the earliest stages gradually diminish and are often largely masked when complete lobar consolidation has developed. Resolution is frequently accompanied by a varying degree of organization of the grosser framework of the lung. A variable amount of organization of the alveolar exudate also may occur.
Extrapolation from ten sections can make CT-based quantification of lung aeration more practicable
Authors: A. W. Reske, A. P. Reske, H. A. Gast, M. Seiwerts, A. Beda, U. Gottschaldt, C. Josten, D. Schreiter, N. Heller, H. Wrigge, M. B. Amato
Journal: Intensive Care Medicine (2010)
Current Concepts of the Genesis of Heart Sounds
Authors: Jonathan Abrams
Journal: JAMA (1978)

IMPORTANT advances in the understanding of heart sound production have been made in recent years. The work of Aldo A. Luisada, MD, and James A. Shaver, MD, and their respective co-workers has been particularly fertile; Pravin M. Shah, MD, Ernest Craige, MD, and Robert J. Adolph, MD, also have made major contributions. This communication summarizes current concepts of heart sound genesis; areas of unresolved controversy remain, and additional research may further modify our present thinking. <h3>A UNIFIED CONCEPT</h3> Most investigators now agree that all four cardiac sounds result from vibrations of cardiac structures produced by acceleration and deceleration of the blood mass.<sup>1</sup>This view, first emphasized by Robert F. Rushmer, MD, stresses that the muscle mass of the left ventricle (LV), the cardiac skeleton, the valves, and the great vessels are all set into vibration by the momentum and velocity of the fluid-filled elastic system during phases of the
Cystic fibrosis transmembrane conductance regulator mutations that disrupt nucleotide binding.
Authors: J Logan, D Hiestand, P Daram, Z Huang, D D Muccio, J Hartman, B Haley, W J Cook, E J Sorscher
Journal: Journal of Clinical Investigation (1994)

Increasing evidence suggests heterogeneity in the molecular pathogenesis of cystic fibrosis (CF). Mutations such as deletion of phenylalanine at position 508 (delta F508) within the cystic fibrosis transmembrane conductance regulator (CFTR), for example, appear to cause disease by abrogating normal biosynthetic processing, a mechanism which results in retention and degradation of the mutant protein within the endoplasmic reticulum. Other mutations, such as the relatively common glycine-->aspartic acid replacement at CFTR position 551 (G551D) appear to be normally processed, and therefore must cause disease through some other mechanism. Because delta F508 and G551D both occur within a predicted nucleotide binding domain (NBD) of the CFTR, we tested the influence of these mutations on nucleotide binding by the protein. We found that G551D and the corresponding mutation in the CFTR second nucleotide binding domain, G1349D, led to decreased nucleotide binding by CFTR NBDs, while the delta F508 mutation did not alter nucleotide binding. These results implicate defective ATP binding as contributing to the pathogenic mechanism of a relatively common mutation leading to CF, and suggest that structural integrity of a highly conserved region present in over 30 prokaryotic and eukaryotic nucleotide binding domains may be critical for normal nucleotide binding.
Response to cardiac resynchronization therapy in elderly patients (≥70 years) and octogenarians
Authors: Frederik H. Verbrugge, Matthias Dupont, Philippe de Vusser, Maximo Rivero‐Ayerza, Hugo Van Herendael, Jan Vercammen, Linda Jacobs, David Verhaert, Pieter Vandervoort, W.H. Wilson Tang, Wilfried Mullens
Journal: European Journal of Heart Failure (2012)