tbuckley/cabot-search huggingface dataset:
ACID EXCRETION IN RUBIDIUM- AND CESIUM-SUBSTITUTED RATS*†
Authors: Philip W. Hall, Arnold S. Relman
Journal: Journal of Clinical Investigation (1960)

Previous studies have shown that rubidium or cesium can replace a major part of intracellular cation in vivo, and can correct the extracellular alkalosis associated with potassium depletion (1).In nephrectomized potassium-deficient animals it was demonstrated that rubidium, like potassium, lowers extracellular bicarbonate concentration by displacement of intracellular protons (2) [the latter perhaps transported out of cells by cationic amino acids (3)].However, clear quantitative differences can be demonstrated between the ef- fects of rubidium and potassium on extracellular bicarbonate: a) chronic administration of RbC1 to potassium-deficient alkalotic rats results in extra- cellular acidosis, whereas an equivalent amount of KCl merely restores extracellular bicarbonate concentration to normal (2); and b) acute loading of normal rats with RbCl produces a much greater reduction in extracellular bicarbonate than does an equivalent load of KCl (4).A remarkable feature of the extracellular acido- sis produced in normal rats by acute loading with RbCl is the absence of any immediate renal com- pensation (4).Despite reduction of plasma CO2 content to 13 mMoles per L. there was no reduction in urine pH, and a slight fall, rather than an increase, in ammonium excretion.Since the ad- ministration of acid loads to rats ordinarily re- sults in immediate and very large increments in acid excretion (5-7), the present study was undertaken to learn more about this apparently anom- alous behavior of the rubidium-loaded kidney.
Pregnancy associated plasma protein-A is preferentially expressed in plaque of patients with restenosis
Authors: Ali E. Denktas, Kristen Shogren, David R. Holmes, Antoni Bayes-Genis, Claus Oxvig, Michael T. Overgaard, Michael Christiansen, Cheryl A. Conover, Robert S. Schwartz
Journal: Journal of the American College of Cardiology (2002)
Immunogenicity of Inactivated Parainfluenza Type 1, Type 2, and Type 3 Vaccines in Infants
Authors: Hyun Wha Kim
Journal: JAMA (1966)

Inactivated viral vaccines for parainfluenza virus types 1, 2, and 3 were prepared in embryonated hens' eggs, type 1 in the allantoic cavity, types 2 and 3 in the amniotic sac. The vaccines were given to 36 young infants, 28 of whom lacked neutralizing antibody for the virus corresponding to the vaccine administered. Ten infants received parainfluenza 1, ten received parainfluenza 2, and 16 received parainfluenza 3 vaccine. All infants received two injections at an interval of one month, and each infant given the parainfluenza 1 and 3 vaccines received an additional injection 41 to 163 days after the second injection. These vaccines were 90% to 100% effective in inducing a neutralizing antibody response. The infants given parainfluenza 2 vaccine responded following two injections, whereas a majority of those given parainfluenza 1 and 3 vaccines required an additional injection at a later time. Repeated freezing and thawing appeared to inactivate the serum neutralizing activity induced by type 2 vaccine.
Prevention of rhinovirus infection in chimpanzees by soluble intercellular adhesion molecule-1.
Authors: E D Huguenel, D Cohn, D P Dockum, J M Greve, M A Fournel, L Hammond, R Irwin, J Mahoney, A McClelland, E Muchmore, A C Ohlin, P Scuderi
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Intercellular adhesion molecule-1 (ICAM-1) is the cell surface receptor for the major class of human rhinoviruses, and tICAM453, a truncated, soluble form of ICAM-1, has been shown previously to be a potent in vitro inhibitor of rhinovirus. In this report, we have investigated the in vivo efficacy of tICAM453 for the prophylaxis of rhinovirus serotype 16 infection in the chimpanzee. Because chimpanzees do not show clinical symptoms of infection after rhinovirus challenge, infection was followed by measuring antirhinovirus serum antibody responses and detection of virus shedding. By both of these measures, intranasal application of tICAM453 was efficacious in preventing rhinovirus infection in chimpanzees subsequently challenged with infectious doses of virus. These results suggest that the use of soluble rhinovirus receptor to inhibit virus binding to host cells should be feasible in humans.
Immunopathology of Uveitis: A Symposium Sponsored by the Council for Research in Glaucoma and Allied Diseases, Alfred P. Sloan Foundation, Inc., 630 Fifth Avenue, New York 20, New York, September 3, 4 and 5, 1963
Authors: David Shoch
Journal: JAMA (1965)

The subject of uveitis is a most depressing one for the average ophthalmologist. He knows full well that in spite of intensive investigation he will rarely find the etiology of the patient's problem, and the internist to whom he refers the patient for a "complete work-up" is equally distressed by his inability to aid his ophthalmologic colleague, even after wide dispersal of the patient's funds to various laboratories. This book, the transcription of a symposium held in September 1963, offers some cheer to the ophthalmologists, internists, and immunologists who are interested in uveitis. The participants are a "Who's Who" of immunology and ophthalmology. To mention a few—Blodi of Iowa, Feldman and Leopold of New York, Hogan and Kimura of California, Kaufman of Florida, Silverstein and Zimmerman of the Armed Forces Institute of Pathology, Witebsky of Buffalo, and Witmer of Switzerland. These men and others under the direction of Maumenee of
Vorinostat and Sorafenib Synergistically Kill Tumor Cells via FLIP Suppression and CD95 Activation
Authors: Guo Zhang, Margaret A. Park, Clint Mitchell, Hossein Hamed, Mohamed Rahmani, Aditi Pandya Martin, David T. Curiel, Adly Yacoub, Martin Graf, Ray Lee, John D. Roberts, Paul B. Fisher, Steven Grant, Paul Dent
Journal: Clinical Cancer Research (2008)

Abstract Purpose and Design: Mechanism(s) by which the multikinase inhibitor sorafenib and the histone deacetylase inhibitor vorinostat interact to kill hepatic, renal, and pancreatic adenocarcinoma cells has been defined. Results: Low doses of sorafenib and vorinostat interacted in vitro in a synergistic fashion to kill hepatic, renal, and pancreatic adenocarcinoma cells in multiple short-term viability (24-96 h) and in long-term colony formation assays. Cell killing was suppressed by inhibition of cathepsin proteases and caspase-8 and, to a lesser extent, by inhibition of caspase-9. Twenty-four hours after exposure, the activities of extracellular signal-regulated kinase 1/2, AKT, and nuclear factor-κB were only modestly modulated by sorafenib and vorinostat treatment. However, 24 h after exposure, sorafenib- and vorinostat-treated cells exhibited markedly diminished expression of c-FLIP-s, full-length BID, BCL-2, BCL-XL, MCL-1, XIAP, increased expression of BIM, and increased activation of BAX, BAK, and BAD. Expression of eIF2α S51A blocked sorafenib- and vorinostat-induced suppression of c-FLIP-s levels and overexpression of c-FLIP-s abolished lethality. Sorafenib and vorinostat treatment increased surface levels of CD95 and CD95 association with caspase-8. Knockdown of CD95 or FADD expression significantly reduced sorafenib/vorinostat-mediated lethality. Conclusions: These data show that combined exposure of epithelial tumor cell types to sorafenib and vorinostat diminishes expression of multiple antiapoptotic proteins and promotes activation of the CD95 extrinsic apoptotic and the lysosomal protease pathways, and that suppression of c-FLIP-s expression represents a critical event in transduction of the proapoptotic signals from CD95 to promote mitochondrial dysfunction and death.
Alpha–1–Antitrypsin Distribution in Nodular Regenerative Hyperplasia of Liver
Authors: Swan N. Thung
Journal: Hepatology (1990)

Nodular regenerative hyperplasia, a disorder characterized by regenerative nodules scattered diffusely throughout the liver without associated fibrosis, is most often recognized at autopsy when the entire liver is available for inspection. Diagnosis by needle biopsy is much more subtle. Because alpha–1–antitrypsin expression by hepatocytes in a variety of liver diseases has suggested that it may represent a marker for regenerative or damaged hepatocytes, we elected to study the expression of alpha– 1 –antitrypsin by immunohisto chemical staining of paraffin–embedded tissue of biopsy material as a possible marker of this diagnosis. Seventeen liver biopsy specimens showing histological features consistent with nodular regenerative hyperplasia were selected and compared with 20 biopsy specimens of the liver without such features. Eight of the diseased cases showed periportal granular alpha– 1–antitrypsin staining as opposed to only one of the healthy biopsy specimens (p &lt; 0.01; Fisher exact test). These results indicate that alpha–1–antitrypsin expression is increased in the regenerating compartment (as opposed to the presumably damaged atrophic portion) of the liver in nodular regenerative hyperplasia and suggest that alpha–1–antitrypsin staining may be useful in confirming the diagnosis of the disease by biopsy specimens.
P518Biomechanical properties, microstructure and constitutive modeling of human ventricular myocardium
Authors: G Sommer, M Schwarz, AJ Schriefl, H Wolinski, S Kohlwein, C Viertler, P Regitnig, GA Holzapfel
Journal: Cardiovascular Research (2014)

In the multidisciplinary field of heart research it is of utmost importance, for the description of phenomena like mechanoelectric feedback or heart wall thickening, to identify accurate myocardium material properties. Therefore this study aims to determine biaxial tensile and triaxial shear properties of the passive human ventricular myocardium. This novel combination of biaxial and shear testing, together with the investigation of the myocardial microstructure, will yield new innovative and essential information about material properties to fulfil the short term goals of constructing realistic myocardial models capable of capturing the mechanics of the heart, as well as aiding the long term goals of improving methods of medical treatment and quality of life for people suffering from heart diseases. For the biaxial tests, squared specimens (25x25x2mm) were prepared with their sides aligned with the fiber and cross-fiber axis. During the experiments, the specimens were submerged in a cardioplegic solution at physiological conditions and different stretch ratios were applied consecutively. For the triaxial shear testing, three adjoining cubic specimens (4x4x4mm) were prepared with their sides aligned according to the fiber axis, sheet axis and sheet-normal axis. Three cycles of sinusoidal simple shear (0.1-0.5 in 0.1 steps of specimen thickness) were applied to each cubic specimens in two orthogonal directions. A novel combination of optical clearing and multiphoton microscopy was utilized to explore the 3D microstructure of the tissue emphasizing the 3-D orientation and dispersion of the muscle fibers and adjacent collagen fabrics. The tissue showed pronounced nonlinear and highly orientation dependent behavior. The donor's age was greatly influencing the mechanical behavior of the myocardial tissue. Microstructural investigations affirmed an orthotropic composition of the investigated tissue and showed highly aligned myofibers with small dispersion in the healthy human myocardium. An invariant-based constitutive model showed the ability to give a good representation of both the biaxial tensile and the triaxial shear responses. The material data from this study is intended to be used in numerical (Finite Element) simulations for better understanding of fundamental underlying ventricular mechanics, a step needed in the improvement of medical treatment of heart diseases.
Is epidermal cell proliferation in psoriatic skin grafts on nude mice driven by T-cell derived cytokines?
Authors: B.S. BAKER, L. BRENT, H. VALDIMARSSON, A.V. POWLES, L. AL-IMARA, M. WALKER, L. FRY
Journal: British Journal of Dermatology (1992)

Plasminogen activity and DNA synthesis by epidermal cells have been reported to be doubled in psoriatic skin grafts compared with grafts of normal skin 6 weeks after transplantation to nude mice. In our study human lymphocytes disappeared from such grafts within 48 h whilst some DR-positive human dendritic cells were retained in the grafts for up to 4 weeks. However, the grafts were infiltrated by Thy 1.2+ mouse lymphocytes within 6 days and this infiltration persisted at a moderate level throughout the observation period. It consisted of perivascular aggregates, scattered dermal and papillary T cells, and some mouse T cells were also found in the epidermal compartment. Grafts of psoriatic and non-psoriatic control skin were infiltrated to a similar extent, suggesting a low-grade rejection response against the human xenografts. These findings raise the possibility that psoriatic keratinocytes are responding abnormally to inflammatory cytokines released by mouse lymphocytes reacting against the skin grafts.
Renal Effects of Calcitonin
Authors: M. Cochran, M. Peacock, G. Sachs, B. E. C. Nordin
Journal: BMJ (1970)

Porcine calcitonin in a slow-release gelatin vehicle was given by intramuscular injection to 10 patients-four with primary hyperparathyroidism, four with Paget's disease, and two with carcinoma of the breast and hypercalcaemia. All cases showed a fall in serum calcium with an immediate rise in urine calcium. All except three patients with primary hyperparathyroidism showed a fall in serum phosphorus, but an immediate rise in urine phosphorus occurred in all cases. Urine hydroxyproline output fell in three patients with severe Paget's disease. Urine sodium rose in all cases, but the effects on potassium, magnesium, water, and pH were not appreciably different from results obtained in four control subjects who were given the gelatin vehicle alone.The data suggest that calcitonin caused a decrease in the tubular resorption of calcium and phosphorus. The hypocalcaemic effect appeared to be due to a decrease in bone resorption in the patients with Paget's disease but in the remaining cases could be accounted for in part or entirely by the rise in urine calcium.
For Mutual Improvement in the Healing Art
Authors: Whitfield J. Bell
Journal: JAMA (1971)

The commencement exercises of  College of Philadelphia were held in  spring of 1768. As  provost of  institution,  Reverend Dr. William Smith turned to confer degrees of bachelor of medicine on ten young men who had completed  course of instruction, he proudly assured his audience that this was the Birth-day of Medical Honours in America. It was that indeed—the first graduation of  first medical school in  British North American colonies;  culmination of some years of dreaming and effort; another evidence, if one were needed, of  increasing social and cultural maturity of  colonies.  Additional evidence that in  third quarter of  18th century  American medical profession was becoming mature we find in  professional societies which began to be established. In a few towns before 1750, to be sure, physicians had formed societies for mixed professional and social purposes;
Computerised evidence based guidelines in primary care: Computerised decision support and reflection in action
Authors: T. Lipman
Journal: BMJ (2003)

EDITOR—Eccles et al have shown not only the lack of effectiveness of a computerised decision support system based on evidence based guidelines but also some of the reasons why general practitioners found it unusable in everyday clinical practice.1 2

General practitioners value information on demand but need to be able to recognise the need for information and to possess the skills to obtain …
Abstract 3307: The multitasking of Sox2: Maintaining the stemness and inducing the malignant phenotype of gliomas
Authors: Marta M. Alonso, Lorea Manterola, Ricardo Diez-Valle, Nahir Cortes-Santiago, Dan Liu, Angel Rubio, Jesus Garcia-Foncillas, Miguel Angel Idoate, Juan Fueyo, Candelaria Gomez-Manzano
Journal: Cancer Research (2011)

Abstract Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, displays an enrichment gene expression related to a stem cell signature. Sox2, a major stemness factor involved in pluripotency and in the maintenance of neural stem cell identity, has been described as frequently overexpressed in poorly differentiated gliomas. However, the role that this molecule plays in brain tumors remains under investigation. In this study, we sought to ascertain the Sox2 potential function in the control of self-renewal of brain tumor stem cells (BTSCs) and the malignant phenotype of gliomas. Our results showed Sox2 expression in human surgical malignant gliomas. In addition, Sox2 expression was significantly higher in the BTSC lines than in established glioma cell lines. Downmodulation of Sox2 in BTSCs by using siRNA resulted in the loss of the self-renewal properties of this cell population, and modification in the pattern of expression of markers related with stem cells properties and differentiation. These results are of major importance since, in the TCGA, we observed Sox2 overexpression in more than 80% of the samples (n=188), gene amplification of SOX2 in 18% of the individuals, and hypomethylation of the promoter in about 90% of the samples when compared with normal tissue, suggesting the relevance of this transcription factor in the malignant phenotype of GBMs. In this regard, our results demonstrated that SOX2 plays a prominent role in the invasive and migratory capabilities of both BTSCs and established glioma cell lines. Thus, ectopic expression of Sox2 was sufficient to induce invasion of glioma cells and knockdown experiments demonstrated that Sox2 is essential for maintaining the invasive properties of glioma cells. Therefore, these results identify a multi-functional aspect of Sox2 as both, a stemness promoting molecule and an essential pro-invasive protein, elucidating the possibility of targeting Sox2 for glioma therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3307. doi:10.1158/1538-7445.AM2011-3307
Efficacy of 99mTc-WBC Imaging in Detection of Prosthetic Vascular Graft Infection
Authors: Simin Dadparvar, Christopher I. Kaufman, Lalitha Krishna, Muhammad M. Gillan, Kiran M. Kapadia, Jingbo Wang, Walter J. Slizofski, Teruo Matsumoto
Journal: Clinical Nuclear Medicine (1997)

Dadparvar, Simin M.D.; Kaufman, Christopher I. B.S.; Krishna, Lalitha M.D.; Gillan, Muhammad M. M.D.; Kapadia, Kiran M. M.D.; Wang, Jingbo M.D.; Slizofski, Walter J. M.D.; Matsumoto, Teruo M.D. Author Information
Preoperative Parathyroid Localization
Authors: Richard H. Egdahl
Journal: New England Journal of Medicine (1979)

Edis and Evans describe in this week's issue the use of high-resolution ultrasonography to localize parathyroid tumors before operation. From the standpoint of the parathyroid surgeon, a procedure that could identify the parathyroids preoperatively and indicate which glands were diseased would be valuable. However, in most cases an experienced surgeon can find the four glands quite rapidly and identify any gross abnormalities. The basic question about diagnostic ultrasonography is whether it can help in the difficult cases in which the diseased gland is situated in an unusual location or is only slightly enlarged.Several methods for localization have been tried . . .
Compartment-Selective Sensitivity of Cardiovascular Morphogenesis to Combinations of Retinoic Acid Receptor Gene Mutations
Authors: Robin Y. Lee, Jiangming Luo, Ronald M. Evans, Vincent Giguere, Henry M. Sucov
Journal: Circulation Research (1997)

Several aspects of normal cardiovascular development require signaling by the vitamin A metabolite retinoic acid. We have previously established germ-line mutations in mice in the genes that encode the RAR alpha 1, RAR beta, and RXR alpha retinoic acid receptors as a means of studying the function of these receptors in vivo. Although mutation of RXR alpha results in fetal ventricular defects, the RAR alpha 1 and RAR beta mutations are apparently nonphenotypic in the heart and elsewhere. In this study, we have established and analyzed combinations of these receptor gene mutations. Malformations of the ventricular chamber (chamber hypoplasia and muscular ventricular septal defects), conotruncus (double-outlet right ventricle, transposition, and membranous ventricular septal defects), aortic sac (persistent truncus arteriosus and aorticopulmonary window), and aortic arch-derived arteries were recovered in various combinations of the RAR alpha 1, RAR beta, and RXR alpha gene mutations. Depending on the combination of receptor mutations, selective defects were obtained in specific cardiovascular compartments, suggestive of differential expression or function of each receptor within domains of the developing heart.
Patterns of evolution in human speech processing and animal communication
Authors: Michael J. Ryan, Nicole M. Kime, Gil G. Rosenthal
Journal: Behavioral and Brain Sciences (1998)

We consider Sussman et al.'s suggestion that auditory biases for processing low-noise relationships among pairs of acoustic variables is a preadaptation for human speech processing. Data from other animal communication systems, especially those involving sexual selection, also suggest that neural biases in the receiver system can generate strong selection on the form of communication signals.
Posttranscriptional destabilization of the liver-specific long noncoding RNA <i>HULC</i> by the IGF2 mRNA-binding protein 1 (IGF2BP1)
Authors: Monika Hämmerle, Tony Gutschner, Hannah Uckelmann, Sevim Ozgur, Evgenij Fiskin, Matthias Gross, Britta Skawran, Robert Geffers, Thomas Longerich, Kai Breuhahn, Peter Schirmacher, Georg Stoecklin, Sven Diederichs
Journal: Hepatology (2013)

Selected long noncoding RNAs (lncRNAs) have been shown to play important roles in carcinogenesis. Although the cellular functions of these transcripts can be diverse, many lncRNAs regulate gene expression. In contrast, factors that control the expression of lncRNAs remain largely unknown. Here we investigated the impact of RNA binding proteins on the expression of the liver cancer-associated lncRNA HULC (highly up-regulated in liver cancer). First, we validated the strong up-regulation of HULC in human hepatocellular carcinoma. To elucidate posttranscriptional regulatory mechanisms governing HULC expression, we applied an RNA affinity purification approach to identify specific protein interaction partners and potential regulators. This method identified the family of IGF2BPs (IGF2 mRNA-binding proteins) as specific binding partners of HULC . Depletion of IGF2BP1, also known as IMP1, but not of IGF2BP2 or IGF2BP3, led to an increased HULC half-life and higher steady-state expression levels, indicating a posttranscriptional regulatory mechanism. Importantly, HULC represents the first IGF2BP substrate that is destabilized. To elucidate the mechanism by which IGF2BP1 destabilizes HULC, the CNOT1 protein was identified as a novel interaction partner of IGF2BP1. CNOT1 is the scaffold of the human CCR4-NOT deadenylase complex, a major component of the cytoplasmic RNA decay machinery. Indeed, depletion of CNOT1 increased HULC half-life and expression. Thus, IGF2BP1 acts as an adaptor protein that recruits the CCR4-NOT complex and thereby initiates the degradation of the lncRNA HULC . Conclusion: Our findings provide important insights into the regulation of lncRNA expression and identify a novel function for IGF2BP1 in RNA metabolism. (Hepatology 2013;58:1703–1712)