tbuckley/cabot-search huggingface dataset:
Lipid-based Nanoparticle Delivery of Pre-miR-107 Inhibits the Tumorigenicity of Head and Neck Squamous Cell Carcinoma
Authors: Longzhu Piao, Manchao Zhang, Jharna Datta, Xiujie Xie, Tizhi Su, Hong Li, Theodoros N Teknos, Quintin Pan
Journal: Molecular Therapy (2012)

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. Our laboratory showed that miR-107 expression is reduced and functions as a tumor suppressor gene in HNSCC suggesting the potential application of miR-107 as a novel anticancer therapeutic. In this study, we determined the efficiency and efficacy of cationic lipid nanoparticles to deliver pre-miR-107 (NP/pre-miR-107) in HNSCC cells in vitro and in vivo. NP/pre-miR-107 increased delivery of miR-107 into HNSCC cells by greater than 80,000-fold compared to free pre-miR-107. Levels of known miR-107 targets, protein kinase Cε (PKCε), cyclin-dependent kinase 6 (CDK6), and hypoxia-inducible factor 1-β (HIF1-β), decreased following NP/pre-miR-107 treatment. Clonogenic survival, cell invasion, and cell migration of HNSCC cells was inhibited with NP/pre-miR-107. Moreover, NP/pre-miR-107 reduced the cancer-initiating cell (CIC) population and dampened the expression of the core embryonic stem cell transcription factors, Nanog, Oct3/4, and Sox2. In a preclinical mouse model of HNSCC, systemic administration of NP/pre-miR-107 significantly retarded tumor growth by 45.2% compared to NP/pre-miR-control (P < 0.005, n = 7). Kaplan-Meier analysis showed a survival advantage for the NP/pre-miR-107 treatment group (P = 0.017). Our results demonstrate that cationic lipid nanoparticles are an effective carrier approach to deliver therapeutic miRs to HNSCC.
Determination of sIgE to rPhl p 1 is sufficient to diagnose grass pollen allergy
Authors: D. Bokanovic, W. Aberer, W. Hemmer, A. Heinemann, P. Komericki, J. Scheffel, G. J. Sturm
Journal: Allergy (2013)

Background New diagnostic tools such as the basophil activation test (BAT) and component-resolved diagnosis (CRD) are promising for hymenoptera venom or food allergy. A clear benefit for inhalant allergens has not yet been shown. Our aim was to compare new and established tests for grass pollen allergy. Methods Forty-nine patients with grass pollen allergy and 47 controls were prospectively enrolled in the study. A symptom score was calculated for each patient. Conjunctival provocation tests (CPT), skin prick tests (SPT), BAT, and sIgE determination including CRD were performed. Sensitivity and specificity were compared and results were correlated with the symptom score. Results Single determination of sIgE to rPhl p 1 showed the best balance between sensitivity (98%) and specificity (92%). Use of additional components, such as rPhl p 2 and 5, did not increase sensitivity. Generally, sensitivity of tests was high: SPT 100%, ISAC-112 100%, sIgE to timothy grass 98%, BAT 98%, ISAC-103 84%, and CPT 83%. Specificity ranged from 79% (SPT) to 96% (CPT). All test results and calculated values (e.g. ratio sIgE/tIgE) did not correlate with symptom severity. Asymptomatic sensitization to timothy grass in controls was rare in the CAP (11%) and predominantly due to Phl p 1 sensitization. Conclusion rPhl p 1 was sufficient to diagnose grass pollen allergy, and sIgE patterns were the same in symptomatically and asymptomatically sensitized subjects. The testing of multiple components was of minor importance, and no test correlated with symptom severity.
The addition of a protease inhibitor increases the risk of infections in patients with hepatitis C-related cirrhosis
Authors: Maria-Carlota Londoño, Christie Perelló, Joaquín Cabezas, Nuria Cañete, Sabela Lens, Zoe Mariño, Martina Gambato, Raquel Rodríguez, Susana Menéndez, José A. Carrión, Javier Crespo, José Luis Calleja, Xavier Forns
Journal: Journal of Hepatology (2014)
The effect of sequestration by nontarget tissues on anti-tumor efficacy of systemically applied, conditionally replicating adenovirus vectors
Authors: Kathrin M Bernt, Shaoheng Ni, Zong-Yi Li, Dmitry M Shayakhmetov, André Lieber
Journal: Molecular Therapy (2003)

Avoiding transduction of normal tissue after intravenous application of oncolytic adenoviruses (Ad) is an important strategy to improve the safety and efficacy of these vectors in gene therapy. As a model for a targeted vector, we used Ad vectors with type 35 fibers (Ad5/35), which efficiently transduce human cervical carcinoma cells but not liver cells. In an in vitro model of liver metastases, in which small nests of HeLa cells were surrounded by mouse hepatocytes, we showed that an Ad5/35-based conditionally replicating vector regulated by DNA replication-dependent recombination conferred increased gene transfer to tumor cells and enhanced viral replication and tumor cell lysis compared to the nontargeted Ad5 vector. Intravenous injection of Ad5/35 vectors into mice bearing liver metastases derived from HeLa cells caused markedly less hepatotoxicity than Ad5 vectors; however, it did not result in enhanced tumor cell transduction, viral replication, or oncolysis. Apparently, other factors, including the stability of virus in the blood, trapping within the liver sinusoids, transendothelial transfer, and/or vector diffusion of viral particles to tumor cells, limit tumor transduction, even if the vector is not taken up by liver cells.
Plasma and Urine Cyclic Guanosine 3′:5′-Monophosphate in Disseminated Cancer
Authors: Rajender K. Chawla, Daniel W. Nixon, Mamoru Shoji, Daniel Rudman
Journal: Annals of Internal Medicine (1979)

Plasma and 24-h urinary adenosine 3′:5′-monophosphate (cyclic AMP) and guanosine 3′:5′-monophosphate (cyclic GMP) were measured by radioimmunoassay in 12 normal subjects, 33 patients with six types of non-neoplastic disease (cholelithiasis, peptic ulcer, coronary heart disease, hypertension, regional ileitis, and cirrhosis), and 34 patients with five types of disseminated neoplastic disease (acute myelocytic leukemia; Hodgkin's disease; and metastatic cancer of the lung, colon, and breast). In patients with non-neoplastic disease, cyclic nucleotide values in plasma and urine did not differ significantly (P > 0.05) from those in normal subjects. In patients with disseminated cancer, cyclic AMP values in plasma and urine likewise did not differ significantly from those in normal subjects. Plasma cyclic GMP, in contrast, was significantly elevated in all five types of cancer patients, and urinary cyclic GMP was significantly elevated (five times the normal mean) in patients with acute myelogenous leukemia and Hodgkin's disease.
Neutrophil adherence to isolated adult canine myocytes. Evidence for a CD18-dependent mechanism.
Authors: M L Entman, K Youker, S B Shappell, C Siegel, R Rothlein, W J Dreyer, F C Schmalstieg, C W Smith
Journal: Journal of Clinical Investigation (1990)

Cardiac myocytes were isolated from adult dogs and incubated with isolated canine neutrophils (PMN). Intercellular adhesion was low and unchanged by stimulation of the PMN with zymosan activated serum or platelet activating factor (PAF) at concentrations that significantly enhance PMN adhesion to protein-coated glass and canine endothelial cell monolayers. Intercellular adhesion was significantly increased only when both myocytes and PMN were stimulated (e.g., myocytes incubated with IL-1, tumor necrosis factor, or phorbol myristate acetate, and PMN were chemotactically stimulated). Inhibitors of protein synthesis diminished the IL-1 beta-induced effect by greater than 80%. The IL-1 beta, PAF-stimulated PMN-myocyte adhesion was associated with substantial H2O2 production. Under conditions with low PMN-myocyte adhesion (i.e., IL-1 beta alone, PAF alone, or no stimulus) H2O2 production was generally less than 5% of that occurring with high adhesion. An anti-CD18 monoclonal antibody (R15.7) inhibited stimulated PMN-myocyte adhesion by greater than 95% and reduced H2O2 production by greater than 90%. Control isotype-matched, binding, and nonbinding antibodies were without effect on adherence or H2O2 production. The results indicate that cytokine stimulation of adult myocytes induces expression of a ligand involved in CD18-dependent adherence of canine neutrophils.
More Names for Depression: Is a Rose a Rose?-Reply
Authors: Robert M. A. Hirschfeld
Journal: JAMA (1997)

<h3>In Reply.</h3> —Dr Reynolds has come forward with a fascinating proposal—to rename clinical depression as "limbic dysfunction." His reasoning is that control or mediation of many of the symptoms of depression are located in limbic structures. His proposal is worthy of serious consideration I certainly agree that depression is a disorder of regulation, but I think it would be a mistake to reference this primarily to the limbic system. We have evidence that abnormalities in other areas of the brain (the frontal cortex and the caudate nucleus) are associated with depression.<sup>1-3</sup>Furthermore, depression is a whole-body illness. For example, endocrinologic abnormalities are not restricted to the brain. Also, the proposal of limbic dysfunction ignores important cognitive (eg, feelings of worthlessness) and interpersonal (eg, social with-drawal and impaired relationships) features that are fundamental to depression. I would prefer to renew efforts at destigmatizing medical illnesses that have behavioral and emotional components
Pathogenesis of Salmonellosis STUDIES OF FLUID SECRETION, MUCOSAL INVASION, AND MORPHOLOGIC REACTION IN THE RABBIT ILEUM
Authors: R. A. Giannella, S. B. Formal, G. J. Dammin, H. Collins
Journal: Journal of Clinical Investigation (1973)

Strains of Salmonella typhimurium were studied in the ligated rabbit ileal loop model to gain insight into the mechanisms whereby bacteria which invade the gastrointestinal mucosa evoke fluid exsorption. The organisms employed differed in various biologic attributes including the ability to invade the ileal epithelium, multiply within the mucosa, elicit an acute inflammatory reaction, and disseminate across the intestinal wall. Some strains provoked small intestinal fluid exsorption although these did not elaborate enterotoxin. Only those strains which invaded the mucosa were accompanied by either mucosal inflammation or fluid exsorption. Noninvasive strains produced neither histologic abnormalities nor fluid secretion. While strains which invaded the mucosa caused an acute inflammatory reaction, not all such strains evoked fluid secretion. Furthermore, there was no correlation in ability of invasive organisms to evoke fluid secretion or in the intensity of mucosal inflammation, number of intramucosal salmonellae, or in ability to disseminate from the rabbit ileum. These observations suggest that, as is the case in shigellosis, mucosal invasion may be a necessary factor for the intestinal fluid loss in salmonellosis. A bacterial property or factor, in addition to invasion of the gastrointestinal mucosa, seems to be responsible for fluid exsorptin. However, it is unlikely that a salmonella enterotoxin comparable to that elaborated by Vibrio cholerae, toxigenic Escherichia coli, or Shigella dysenteriae 1 is related to fluid secretion in salmonellosis.
Evaluation of the Efficacy and Safety of Once-a-Day Dosing of Tadalafil 5mg and 10mg in the Treatment of Erectile Dysfunction: Results of a Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Hartmut Porst, François Giuliano, Sidney Glina, David Ralph, Adolfo R. Casabé, Albert Elion-Mboussa, Wei Shen, J. Steve Whitaker
Journal: European Urology (2006)
Clement John (“Jack”) White
Authors: D Davies
Journal: BMJ (2006)

Former consultant anaesthetist Mansfield group of hospitals (b 1924; q The London Hospital 1953; DA, FFARCS), d 22 March 2006.

After leaving school in 1942 Clement White (“Jack”) joined the Royal Electrical and Mechanical Engineers and served for the rest of the war. He then went to The London Hospital; after a series of house jobs he went into general practice. After a year he specialised in anaesthetics, working initially in Reading and later as a senior registrar at St Bartholomew's Hospital. He came to Mansfield in 1963 as a consultant, setting up an intensive care unit at the general hospital. A keen gardener and amateur engineer, he retired in 1989. He leaves a wife and daughter.
Severe hepatitis caused by cyproterone acetate.
Authors: J C Blake, A M Sawyerr, J S Dooley, P J Scheuer, N McIntyre
Journal: Gut (1990)

A case of severe acute hepatitis caused by cyproterone acetate in a 71 year old man with prostatic carcinoma is reported with a review of the literature on hepatic reactions to this drug. The association between the use of cyproterone acetate and liver abnormalities is poorly documented. This is the fourth published report of adverse hepatic reaction to cyproterone acetate and it substantiates other evidence that cyproterone acetate is potentially hepatotoxic. Monitoring of liver function tests should be mandatory in patients receiving high doses of cyproterone acetate; the drug should be withdrawn immediately if abnormal liver function tests are found.
Physician: Healer and Scientist
Authors: John H. Talbott
Journal: JAMA (1961)

Dana Winslow Atchley, M.D., Emeritus Professor of Clinical Medicine at the Columbia-Presbyterian Medical Center, New York City, contributor toThe Saturday Review, Atlantic Monthly, andThe New Yorkerin recent years, and author of a number of scientific periodicals in former years, is well qualified to discuss medicine as a career. Doctor Atchley, son of a Baptist minister, reflects a compassion for student and patient, stemming from his early training in the home and strengthened by almost half a century in the study and practice of medicine. It was interesting to learn that mathematics through calculus was recommended as a premedical requirement. More important is the belief that scholarly achievement is the most important tool a student can acquire in college and medical school-scholarly achievement based upon study in depth, be it physics, Elizabethan literature, or Greek mythology. I do not know whether this little book was designed to lure
Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors
Authors: Katrin Mackarehtschian, Jeff D. Hardin, Katrd A. Moore, Sharon Boast, Stephen P. Goff, Ihor R. Lemischka
Journal: Immunity (1995)

The flk2 receptor tyrosine kinase has been implicated in hematopoietic development. Mice deficient in flk2 were generated. Mutants developed into healthy adults with normal mature hematopoietic populations. However, they possessed specific deficiencies in primitive B lymphoid progenitors. Bone marrow transplantation experiments revealed a further deficiency in T cell and myeloid reconstitution by mutant stem cells. Mice deficient for both c-kit and flk2 exhibited a more severe phenotype characterized by large overall decreases in hematopoietic cell numbers, further reductions in the relative frequencies of lymphoid progenitors, and a postnatal lethality. Taken together, the data suggest that flk2 plays a role both in multipotent stem cells and in lymphoid differentiation.
Prognostic Significance of Sympathetic Nervous System Activation in Pulmonary Arterial Hypertension
Authors: Agnieszka Ciarka, Vi Doan, Sonia Velez-Roa, Robert Naeije, Philippe van de Borne
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Rationale: The sympathetic nervous system has been reported to be activated in pulmonary arterial hypertension (PAH).Objectives: We investigated the prognostic significance of muscle sympathetic nervous system activity (MSNA) in PAH.Methods: Thirty-two patients with PAH were included in the study and underwent a measurement of MSNA over a 6-year period of time. They had undergone a concomitant evaluation of New York Heart Association (NYHA) functional class, a 6-minute walk distance (6MWD), an echocardiographic examination, and a right heart catheterization for diagnostic or reevaluation purposes. The median follow-up time was 20.6 months (interquartile range, 45.8 mo). Clinical deterioration was defined by listing for transplantation or death.Measurements and Main Results: Seventeen patients presented with clinical deterioration. As compared with the 15 others, they had an increased MSNA (80 ± 12 vs. 52 ± 18 bursts/min; P < 0.001) and heart rate (88 ± 17 vs. 74 ± 12 bpm; P = 0.01), a lower 6MWD (324 ± 119 vs. 434 ± 88 m; P < 0.01) and a deteriorated NYHA functional class (3.6 ± 0.5 vs. 2.9 ± 0.8; P < 0.001). The hemodynamic variables were not different. MSNA was directly related to heart rate and inversely to 6MWD. A univariate analysis revealed that increased MSNA and heart rate, NYHA class IV, lower 6MWD, and pericardial effusion were associated with subsequent clinical deterioration. A multivariate analysis showed that MSNA was an independent predictor of clinical deterioration. For every increase of 1 burst/minute, the risk of clinical deterioration during follow-up increased by 6%.Conclusions: Sympathetic nervous system activation is an independent predictor of clinical deterioration in pulmonary arterial hypertension.
Reported management of threatened miscarriage by general practitioners in Wessex.
Authors: C Everett, H Ashurst, I Chalmers
Journal: BMJ (1987)

Questionnaires were sent to all 1432 general practitioners in the Wessex region to obtain information about their current management of bleeding in early pregnancy. A total of 1290 (90%) returned completed questionnaires. These showed widely varying views about the prognostic importance of particular symptoms and physical signs and about elements of management. Although 96% of the respondents prescribed bed rest more or less routinely for heavy bleeding in early pregnancy, only 17% felt it was mandatory, and 32% admitted that they did not believe it affected the outcome. Of the 13% of respondents who prescribed progestogens for threatened miscarriage, most did so on the advice of their local obstetrician. Seventeen per cent of the doctors always admitted women with apparently complete miscarriages to hospital. Twenty nine per cent of the respondents never gave anti-D immunoglobulin to rhesus negative women after a complete miscarriage. Bleeding in early pregnancy is a common problem and more research is required to improve management, particularly the assessment of fetal viability.
Shared Selective Pressures on Fungal and Human Metabolic Pathways Lead to Divergent yet Analogous Genetic Responses
Authors: Haley R. Eidem, Kriston L. McGary, Antonis Rokas
Journal: Molecular Biology and Evolution (2015)

Reduced metabolic efficiency, toxic intermediate accumulation, and deficits of molecular building blocks, which all stem from disruptions of flux through metabolic pathways, reduce organismal fitness. Although these represent shared selection pressures across organisms, the genetic signatures of the responses to them may differ. In fungi, a frequently observed signature is the physical linkage of genes from the same metabolic pathway. In contrast, human metabolic genes are rarely tightly linked; rather, they tend to show tissue-specific coexpression. We hypothesized that the physical linkage of fungal metabolic genes and the tissue-specific coexpression of human metabolic genes are divergent yet analogous responses to the range of selective pressures imposed by disruptions of flux. To test this, we examined the degree to which the human homologs of physically linked metabolic genes in fungi (fungal linked homologs or FLOs) are coexpressed across six human tissues. We found that FLOs are significantly more correlated in their expression profiles across human tissues than other metabolic genes. We obtained similar results in analyses of the same six tissues from chimps, gorillas, orangutans, and macaques. We suggest that when selective pressures remain stable across large evolutionary distances, evidence of selection in a given evolutionary lineage can become a highly reliable predictor of the signature of selection in another, even though the specific adaptive response in each lineage is markedly different.
A piece of my mind. Windows
Authors: F. D. Campion
Journal: JAMA (1989)

It seems to be getting harder and harder for the layperson to make the necessary, crucial medical decisions only he or she can make. Costs have risen, of course. Ethical questions are more complex. And the growth of scientific technology has made many things more difficult to understand. The voice of common sense, of humane reason, does not come through with the strength we might like. Not that I have anything against the strides made in medicine. High-tech medicine stood me in good stead in my first brush with laryngeal cancer 10 years ago, and it seemed to be doing well in managing a recurrence that appeared last fall. But suddenly, this April, as I struggled to recover from radiation therapy, all of my energy, appetite, and strength seemed to go. A CT scan confirmed the worst suspicion: a new tumor was growing in my neck between the airway and
Coronary Arteriography by the Single Catheter Percutaneous Femoral Technique
Authors: FRED W. SCHOONMAKER, SPENCER B. KING
Journal: Circulation (1974)

A new percutaneous femoral method for studying the coronary arteries, left ventricle and saphenous vein bypass grafts using a single catheter has been developed. A #8 French 100 cm polyurethane catheter with wire incorporated and a 45° curved tip has been used in 6,800 patients. This technique combines the speed and simplicity of the percutaneous femoral approach with the safety of the single catheter technique by eliminating multiple catheter and guidewire changes. Manipulation techniques for selective right and left coronary artery and saphenous vein bypass graft injections as well as for left ventriculography are described. In only 10% of the cases has it been necessary to change to a second catheter, and catheterization time has averaged less than 15 minutes. Complications have been infrequent: femoral thrombosis 0.3%, hematoma 0.2%, myocardial infarction 0.04%, cerebrovascular accident 0.03% and death 0.07%. The speed of the technique and the elimination of multiple catheter changes seem to have contributed to the low complication rate.
Contamination with blood during management of epistaxis
Authors: A S. Carney, J. Weir, D. L Baldwin
Journal: BMJ (1995)

The management of medical emergencies is known to expose medical staff to the risks of blood contamination,1 including infection with HIV and hepatitis B virus.2 Epistaxis is one of the commonest otolaryngological emergencies, requiring treatment that may range from simple chemical cautery to major arterial ligation. We assessed the risk of blood contamination to junior medical staff during the treatment of acute epistaxis and determined patient opinion regarding the junior doctors' use of protective clothing.

Fifty consecutive cases of acute epistaxis treated by two junior medical staff were prospectively studied. Clean protective theatre clothing with gloves, mask, full face visor, hat, and apron was worn during …
Myocardial Infarction and Deep-vein Thrombosis
Authors: A. N. Nicolaides, V. V. Kakkar, J. T. G. Renney, P. H. Kidner, D. C. S. Hutchinson, M. B. Clarke
Journal: BMJ (1971)

In a study of 52 patients admitted into the coronary intensive care unit the incidence of deep-vein thrombosis was measured with the <sup>125</sup>I-fibrinogen test. Of these patients 31 were eventually confirmed to be suffering from acute myocardial infarction. This preliminary study showed that in patients with a confirmed infarct who were not treated with anticoagulants the incidence of deep-vein thrombosis was 38% and in those treated it was 5·5%. In patients who were "severely ill" from whatever the cause there was a high incidence of deep-vein thrombosis (68%).