tbuckley/cabot-search huggingface dataset:
Abstract 2084: Tumor suppressor microRNA miR-34 inhibits human pancreatic cancer stem cells
Authors: Wenhua Tang, Qing Ji, Xinbao Hao, Ling Li, DeSano Jeffrey, Eric R. Fearon, Theodore S. Lawrence, Liang Xu
Journal: Cancer Research (2010)

Abstract MicroRNAs (miRNAs) have been implicated in cancer initiation and progression via their ability to affect expression of genes and proteins that regulate cell proliferation and/or cell death. Transcription of the three miRNA miR-34 family members was recently found to be directly regulated by p53. We show that miR-34 directly regulates Notch and Bcl-2, suggesting the possibility of a role for miR-34 in the maintenance and survival of cancer stem cells. We examined the roles of miR-34 in p53-mutant human pancreatic cancer cell lines and the potential link to cancer stem cells. Restoration of miR-34 expression in the cancer cells by miR-34 mimics or lentiviral miR-34 downregulated Bcl-2 and Notch1/2. miR-34 restoration significantly inhibited clonogenic cell growth and invasion, induced apoptosis and G1 and G2/M arrest in cell cycle, and sensitized the cancer cells to chemotherapy and radiation. We identified that CD44+/CD133+ cancer cells are enriched with tumorsphere-forming and tumor-initiating cells or cancer stem/progenitor cells with high levels of Notch/Bcl-2 and loss of miR-34. More significantly, miR-34 restoration led to an 87% reduction of the tumor-initiating cell population, accompanied by significant inhibition of tumorsphere growth in vitro and tumor-initiation in vivo. Our results demonstrate that miR-34 may restore, at least in part, the tumor suppressing function of the p53 in p53-deficient human pancreatic cancer. Our data support that miR-34 may be involved in cancer stem cell self-renewal, potentially via the direct modulation of downstream targets Bcl-2 and Notch, implying that miR-34 may play an important role in cancer stem cell self-renewal and/or cell fate determination. Currently, we are exploring the nanoparticle-targeted delivery of miR-34 to cancer stem cells as a novel molecular therapy for human pancreatic cancer, based on our patented nanobiotechnology which has been approved by FDA for clinical trials. Taken together, our results demonstrate that restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic/gastric cancer with loss of p53-miR34, potentially via inhibiting cancer stem cells. The project is funded by NIH grants CA121830, CA128220 and CA134655 (to L. Xu.). 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 2084.
Royal Brompton Hospital challenges decision to close its heart surgery unit
Authors: C. Dyer
Journal: BMJ (2011)

The children’s heart surgery unit at one of the UK’s leading hospitals is set for closure in “an act of bureaucratic vandalism,” the high court in London has been told.

The accusation by Alan Maclean QC, counsel for the Royal Brompton and Harefield NHS Foundation Trust, came as the trust opened its legal challenge to a decision to recommend shutting the unit at the Royal Brompton in London.

The trust is seeking a judicial review of the conclusion in the Safe and Sustainable consultation on children’s cardiac surgery services that proposes reducing the three services in London …
A SERIES OF CASES PRESENTING MINOR LESIONS IN THE MACULA LUTEA.Read in the Section of Ophthalmology at the Forty-first Annual Meeting of the American Medical Association, held at Nashville, Tenn., May, 1890.
Authors: G. E. DE SCHWEINITZ
Journal: JAMA (1890)

The lesions of the macula lutea which result from myopia, nephritis and diabetes, anæmia and cardiac disease are well known. Haab (Internationaler Ophthalmologen-Congress, Heidelberg, 1888) has classified the remaining diseases of the macula into several groups: 1. Those due to trauma (<i>a</i>) by contusion of the globe without rent in the sclera (<i>commotio retinæ</i>, of Berlin); (<i>b</i>) secondary to penetrating foreign bodies; (<i>c</i>) secondary to a neighboring rupture of the choroid. 2. Those characterized by the general term senile macular disease. 3. Those seen in people of depressed nutrition—anæmia, diseases of the stomach, etc.—having at the same time an hereditary disposition to macular disease; and finally, 4. Those in which no etiological factor within or without the eye is discoverable. In the groups just referred to, at least in the majority of them, a marked failure of central vision is a characteristic symptom. In the series of cases to which
Transduction of Brain by Herpes Simplex Virus Vectors
Authors: Bradford K Berges, John H Wolfe, Nigel W Fraser
Journal: Molecular Therapy (2006)

The ability of attenuated HSV-1 vectors to spread to regions distant from the injection site indicates that the use of a limited number of injection sites will successfully transduce a major portion, if not an entire large brain. However, many questions remain to be answered. Insufficient data is currently available to allow prediction of where a vector will go following injection into a particular site. Further studies to determine if the vector transport documented in small animal brains will scale-up to large animal brains are needed. Are there any brain regions that are refractory to transduction by HSV-1? Can the virus be effectively targeted to certain brain regions while avoiding others? Can the virus remain transcriptionally active in all regions of the brain? Clearly, the potential for widespread brain transduction is an exciting possibility, but much more work will be required to realize this potential.
RATIONALE OF TREATMENT OF TOXIC AND INFECTION PSYCHOSES
Authors: FRANK P. NORBURY
Journal: JAMA (1918)

The clinical interpretation of toxic and exhaustion psychoses rests, primarily, on psychobiologic principles. Of these principles, the modern physiologic concept that living things are transformers, rather than generators of matter and energy, gives us understanding of the term "mechanism" when applied in conservation of energy, on which concept treatment must be founded. The neural mechanisms with their baffling complexities, their problems of functioning, their clinical interpretations, etc., all require familiarity with the physiology of nervous reactions and afford the most inviting field for the research worker today, especially when in this great world's war, the clinical problems in this special field are overwhelming both in intricacy and in numbers. We must, in our approach to the understanding of these problems, keep in mind the three essential points of Sherrington,<sup>1</sup>as regards nervous reactions, namely, first, the natural history of cell life; second, the conduction of the nervous impulse more
Two Point Mutations Increase Targeted Transduction and Stabilize Vector Association of a Modified Retroviral Envelope Protein
Authors: Tatiana Zavorotinskaya, Lorraine M. Albritton
Journal: Molecular Therapy (2001)

The current strategy of targeting retroviral vector transduction by inserting a peptide ligand into the envelope protein has met with several obstacles. These modified proteins redirected vector binding to a new cognate receptor on a specific cell type but gave little or no gene transfer because they did not fuse the vector and target cell membranes. They dissociated readily from vectors and often required coassembly of wild-type envelope protein. Here we report a novel strategy to overcome the fusion and stability defects of modified retroviral envelope proteins. We inserted a prototypic ligand, the receptor binding domain of amphotropic murine leukemia virus, into an ecotropic murine leukemia virus envelope protein mutant containing glutamine 227-to-arginine plus aspartate 243-to-tyrosine substitutions. This modified protein increased transduction redirected to human cells expressing the amphotropic receptor to a level within 10-fold that of wild-type amphotropic virus, an increase of as great as 2000-fold over transduction by modified protein lacking the mutations. In addition to suppressing the fusion defect, these mutations unexpectedly stabilized the association of the modified protein with vector particles. Insertion of clinically relevant ligands into this envelope mutant should improve the efficiency and reliability of retroviral transduction of specific cell types for gene therapy applications.
Anti-chemokine therapy for the treatment of hepatic fibrosis: An attractive approach
Authors: Grant A. Ramm, Kris Kowdley, Geoffrey McCaughan, Christian Trautwein
Journal: Hepatology (2011)

Activation of hepatic stellate cells in response to chronic inflammation represents a crucial step in the development of liver fibrosis. However, the molecules involved in the interaction between immune cells and stellate cells remain obscure. Herein, we identify the chemokine CCL5 (also known as RANTES), which is induced in murine and human liver after injury, as a central mediator of this interaction. First, we showed in patients with liver fibrosis that CCL5 haplotypes and intrahepatic CCL5 mRNA expression were associated with severe liver fibrosis. Consistent with this, we detected Ccl5 mRNA and CCL5 protein in 2 mouse models of liver fibrosis, induced by either injection of carbon tetrachloride (CCl4) or feeding on a methionine and choline–deficient (MCD) diet. In these models, Ccl5−/− mice exhibited decreased hepatic fibrosis, with reduced stellate cell activation and immune cell infiltration. Transplantation of Ccl5-deficient bone marrow into WT recipients attenuated liver fibrosis, identifying infiltrating hematopoietic cells as the main source of Ccl5. We then showed that treatment with the CCL5 receptor antagonist Met-CCL5 inhibited cultured stellate cell migration, proliferation, and chemokine and collagen secretion. Importantly, in vivo administration of Met-CCL5 greatly ameliorated liver fibrosis in mice and was able to accelerate fibrosis regression. Our results define a successful therapeutic approach to reduce experimental liver fibrosis by antagonizing Ccl5 receptors.
Two cases of distinctive exudative discoid and lichenoid chronic dermatosis of Sulzberger and Garbe responding to azathioprine
Authors: K. FREEMAN, M. HEWITT, A. P. WARIN
Journal: British Journal of Dermatology (1984)

We describe two cases of distinctive exudative and lichenoid chronic determatosis of Sulzberger and Garbe which showed rapid resolution with azathioprine therapy, having failed to resolve with oral prednisolone.
Relative Citation Impact of Various Study Designs in the Health Sciences
Authors: Nikolaos A. Patsopoulos
Journal: JAMA (2005)

The relative merits of various study designs and their placement in hierarchies of evidence are often discussed. However, there is limited knowledge about the relative citation impact of articles using various study designs.To determine whether the type of study design affects the rate of citation in subsequent articles.We measured the citation impact of articles using various study designs--including meta-analyses, randomized controlled trials, cohort studies, case-control studies, case reports, nonsystematic reviews, and decision analysis or cost-effectiveness analysis--published in 1991 and in 2001 for a sample of 2646 articles.The citation count through the end of the second year after the year of publication and the total received citations.Meta-analyses received more citations than any other study design both in 1991 (P<.05 for all comparisons) and in 2001 (P<.001 for all comparisons) and both in the first 2 years and in the longer term. More than 10 citations in the first 2 years were received by 32.4% of meta-analyses published in 1991 and 43.6% of meta-analyses published in 2001. Randomized controlled trials did not differ significantly from epidemiological studies and nonsystematic review articles in 1991 but clearly became the second-cited study design in 2001. Epidemiological studies, nonsystematic review articles, and decision and cost-effectiveness analyses had relatively similar impact; case reports received negligible citations. Meta-analyses were cited significantly more often than all other designs after adjusting for year of publication, high journal impact factor, and country of origin. When limited to studies addressing treatment effects, meta-analyses received more citations than randomized trials.Overall, the citation impact of various study designs is commensurate with most proposed hierarchies of evidence.
Increased Alpha-1-Acid Glycoprotein and Lidocaine Disposition in Myocardial Infarction
Authors: PHILIP A. ROUTLEDGE
Journal: Annals of Internal Medicine (1980)

In 15 patients with confirmed myocardial infarction, alpha-1-acid glycoprotein rose significantly from 117 mg/dL at admission to 140 mg/dL at 36 hours (p <0.01), but not in 15 age- and sex-matched patients with chest pain only. Twelve patients were given prolonged infusions of lidocaine (2 mg/min). In patients with myocardial infarction, the rise in plasma α1-acid glycoprotein concentration was associated with increased lidocaine binding and a rise in total lidocaine concentrations between 12 and 48 hours (p < 0.05). Because of the binding changes, however, the rise in free drug concentration (31.2%) was significantly less than the 56.3% rise in total drug level (p < 0.05). No changes in α1-acid glycoprotein or lidocaine disposition were seen between 12 and 48 hours in the control subjects. Our results show that the rise in α1-acid glycoprotein after myocardial infarction is associated with lidocaine accumulation, but increased plasma binding attenuates the rise in free drug. This suggests that the toxicologic implications of lidocaine accumulation may have been exaggerated and therapeutic monitoring of total plasma levels may be misleading.
Glycemic Control and Hypoglycemia: Is the Loser the Winner?
Authors: Charles M. Clark
Journal: Diabetes Care (2009)

In their otherwise excellent editorial, Perlmuter et al. (1) make the following statement: “Thus, in both sexes, the warning signs and symptoms of hypoglycemia are typically not exhibited until blood glucose drops to dangerously low levels.” From the context, one should conclude that this sentence is referring to individuals who have nocturnal hypoglycemia or some other form of neuroendocrine desensitization frequently …
Prospective multicenter trial for the response-adapted treatment of high-grade malignant non-Hodgkin's lymphomas: Updated results of the COP-BLAM/IMVP-16 protocol with randomized adjuvant radiotherapy
Authors: M. Engelhard, P. Meusers, G. Brittinger, N. Brack, W. Dornoff, W. Enne, W. Gassmann, H. Gerhartz, M. Hallek, J. Heise, W. Hettchen, D. Huhn, K. Kabelitz, R. Kuse, E. Lengfelder, F. Ludwig, I. Meuthen, H. Radtke, C. Schadeck, Schöber C., E. Schumacher, W. Siegert, H.-J. Staiger, E. Terhardt, E. Thiel, M. Thomas, T. Wagner, M.G. Willems, W. Wilmanns, T. Zwingers, H. Stein, M. Tiemann, K. Lennert
Journal: Annals of Oncology (1991)
Effects of oxygen on myocardial blood flow and metabolism
Authors: A. C. F. Kenmure, J. McD. Beatson, A. J. V. Cameron, P. W. Horton
Journal: Cardiovascular Research (1971)

The effects of inhalation of oxygen on myocardial blood flow and metabolism were studied in 10 patients with rheumatic or congenital heart disease. Myocardial blood flow was measured by injection of 133Xe into the left ventricle and sampling from the coronary sinus and aorta. Lactate, pyruvate, and oxygen levels were estimated in arterial and coronary venous blood. Intra-arterial pressures, cardiac output, and heart rate were also measured. After oxygen there was a significant fall in heart rate and myocardial blood flow. There were no significant changes in mean arterial blood pressure or cardiac output. Myocardial oxygen uptake was not altered significantly. The effect on lactate extraction and lactate/pyruvate ratios was variable. The results indicate that inhalation of high concentrations of oxygen does not necessarily increase myocardial oxygen availability.
An unusual case of cerebrovascular disease
Authors: E. F Flint
Journal: BMJ (1979)

After allogeneic hematopoietic stem cell transplantation (allo-HCT), donor-derived B cells develop under selective pressure from alloantigens and play a substantiated role in the autoimmune-like syndrome, chronic graft versus host disease (cGVHD). We performed single-cell RNA-Sequencing (scRNA-Seq) of blood B cells from allo-HCT patients and resolved 10 clusters that were distinguishable by signature genes for maturation, activation and memory. Notably, allo-HCT patient memory B cells displayed some striking transcriptional differences when compared to memory B cells from healthy individuals or non-HCT patients, suggesting molecular differences with a propensity for autoreactivity. To inform more specifically about transcriptional programs important for allo-HCT tolerance, we assessed all 10 clusters for differentially expressed genes (DEGs) between patients with Active cGVHD vs. those without disease (No cGVHD). Data reveal insight into DEGs that may influence multiple aspects of B cell function in allo-HCT, leading to chronic B cell activation in Active cGVHD and our observed expansion of potentially pathogenic atypical/age-related memory B cell (ABC) subsets within a B Cell Receptor (BCR)-experienced memory cluster. Data also indicate chronic B-cell activation and diversification in allo-HCT is potentially plastic, and may be manipulated therapeutically. Our findings have implications in understanding how alloreactivity may lead to human autoimmune disease, and identify potentially novel targets for future study and intervention.
Persistence of Spermatozoa in the Lower Genital Tracts of Women
Authors: Eugene M. Silverman
Journal: JAMA (1978)

Cervicovaginal scrapings from 675 women who had volunteered information about the time of their last coitus and their contraceptive and douching practices were stained with Papanicolaou stain and screened for spermatozoa. Generally, as the interval between coitus and preparation of the smears (postcoital interval) increased, the percentage of smears with spermatozoa and the mean number of spermatozoa per smear decreased, but the percentage of spermatozoa with tails did not change significantly. Spermatozoa were found irregularly after the seventh and rarely after the tenth postcoital day. Vaginal douching, pregnancy, use of oral contraceptives, coitus interruptus, condoms, and vasectomy were associated with reduced prevalence of spermatozoa in smears. (<i>JAMA</i>240:1875-1877, 1978)
Lidocaine Overdose and Cardiac Bypass Support
Authors: Curt R. Freed
Journal: JAMA (1985)

To the Editor.—  We would like to propose cardiac bypass as a novel, lifesaving treatment for lidocaine overdose. Prophylactic lidocaine has been advocated for patients with myocardial infarction to prevent arrhythmias. 1,2 While this therapy has not been shown to save lives, the treatment has resulted in an increase in the use of lidocaine and a corresponding increase in the number of accidental overdoses. 3 Low-level lidocaine intoxication is associated with seizures; more massive overdose leads to cardiogenic shock and death.  Because lidocaine is rapidly cleared by the liver if hepatic blood flow can be maintained, we reasoned that death from cardiogenic shock could be prevented if the circulation could be supported by cardiac bypass. Closed chest massage does not provide enough cardiac output to restore hepatic perfusion and lidocaine clearance. 4 We showed that dogs overdosed with 30 mg per kilogram of lidocaine and treated with conventional pharmacotherapy had
Electric Stimulation Device Approved to Treat Obesity
Authors: Tracy Hampton
Journal: JAMA (2015)

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Effects of endothelial denudation and cholesterol feeding on in vivo transport of albumin, glucose, and water across rabbit carotid artery.
Authors: A V Chobanian, J O Menzoian, J Shipman, K Heath, C C Haudenschild
Journal: Circulation Research (1983)

An in vivo system for studying arterial transport was developed which utilized the rabbit carotid artery perfused in vivo with Dulbecco's modified Eagle's medium containing 125I-labeled albumin, [3H]-3-methyl-d-glucose, or tritiated water. The appearance of labeled materials in jugular venous blood was measured serially over 4 hours. Vascular integrity was assessed by scanning electron and transmission microscopy. Maintenance of endothelial integrity appeared dependent on perfusion with nutrient tissue culture medium, use of papaverine to inhibit arterial spasm, and circulation of the medium under pressure. Acute endothelial denudation with a balloon catheter induced an approximate 10-fold increase in plasma concentration of labeled albumin and a 3-fold rise in plasma [3H]-3-methyl-d-glucose activity, compared with results in animals with intact endothelium. Increased appearance of tritiated water in venous blood was also observed in the rabbits with denuded endothelium, although the relative rise was less than that with albumin or glucose. Feeding rabbits a diet containing 1.5% cholesterol for periods of 16-28 weeks produced approximately 10-fold increases in plasma concentration of 125I-labeled albumin after arterial perfusion to levels comparable to those present in chow-fed rabbits with experimental endothelial denudation. The increases in albumin transport with cholesterol feeding occurred even though a relatively small fraction of the intimal surface was involved with lesions. The results suggest that the arterial endothelium provides a relative barrier to albumin and, to a lesser extent, glucose and water. The findings also suggest that cholesterol feeding markedly increases arterial permeability to albumin, to a degree that is disproportionately greater than the extent of atherosclerotic involvement of the intimal surface.
Preliminary Note on some Parasitic Protozoa Found in Cancerous Tumours
Authors: M. A. Ruffer, J. H. Walker
Journal: BMJ (1892)

THE disease designated under the general term of carcinoma has all the appearances of being caused by a living contagium.A carcinomatous tumour begins in a small group of cells, invades the nearest tissues, gradually infects the lymphatic glands and the inner organs, and finally, should the patient only live long enough, extends to every part of the body.Like all living contagia, cancer chooses its soil, avoids cer- tain people, certain races even, and attacks others who, though apparently in perfect health, fall an easy prey to the disease.True, it is very rare to hear of a cancerous person in- fecting another; but this objection may be met with the answer, that the same has been asserted of diseases which are obviously contagious -such as tubercle-simply because