tbuckley/cabot-search huggingface dataset:
Activated Protein Kinase C Isoforms Target to Cardiomyocyte Caveolae
Authors: Vitalyi O. Rybin, Xiaohong Xu, Susan F. Steinberg
Journal: Circulation Research (1999)

Abstract —Protein kinase C (PKC) isoforms constitute an important component of the signal transduction pathway used by cardiomyocytes to respond to a variety of extracellular stimuli. Translocation to distinct intracellular sites represents an essential step in the activation of PKC isoforms, presumably as a prerequisite for stable access to substrate. Caveolae are specialized subdomains of the plasma membrane that are reported to concentrate key signaling proteins and may represent a locus for PKC action, given that PKC activators have been reported to dramatically alter caveolae morphology. Accordingly, this study examines whether PKC isoforms initiate signaling in cardiomyocyte caveolae. Phorbol ester–sensitive PKC isoforms were detected at very low levels in caveolae fractions prepared from unstimulated cardiomyocytes; phorbol 12-myristate 13-acetate (PMA) (but not 4α-PMA, which does not activate PKC) recruited calcium-sensitive PKCα and novel PKCδ and PKCε to this compartment. The subcellular localization of the phorbol ester–insensitive PKCλ isoform was not influenced by PMA. Endothelin also induced the selective translocation of PKCα and PKCε (but not PKCδ or PKCλ) to caveolae. Multiple components of the extracellular signal–regulated protein kinase (ERK) cascade, including A-Raf, c-Raf-1, mitogen-activated protein kinase kinase, and ERK, were detected in caveolae under resting conditions. Although levels of these proteins were not altered by PMA, translocation of phorbol ester–sensitive PKC isoforms to caveolae was associated with the activation of a local ERK cascade as well as the phosphorylation of a ≈36-kDa substrate protein in this fraction. Finally, a minor fraction of a protein that has been designated as a receptor for activated protein kinase C resides in caveolae and (along with caveolin-3) could represent a mechanism to target PKC isoforms to cardiomyocyte caveolae. These studies identify cardiomyocyte caveolae as a meeting place for activated PKC isoforms and their downstream target substrates.
Cromolyn sodium nasal solution in the prophylactic treatment of pollen-induced seasonal allergic rhinitis
Authors: Nathan I. Handelman, Gilbert A. Friday, Howard J. Schwartz, Forrest S. Kuhn, Dwight E. Lindsay, Patricia G. Koors, Ronald P. Moyer, C.Steven Smith, Charles F. Kemper, James R. Nagel, Jeffrey Rosch, Stephen Murphey, D.Lee Miller
Journal: Journal of Allergy and Clinical Immunology (1977)
Plants in Cardiology
Authors: Rex MacAlpin
Journal: JAMA (1993)

We are in an era of sophisticated artificial synthesis of pharmaceuticals and dwindling forests. It is thus appropriate that we be reminded of the debts owed to the plant kingdom for the origin of many medicines used today. In this monograph Dr Hollman describes the plants from which were derived some of the drugs most commonly used today in cardiology. For each he gives a historical synopsis of the work that led from a chemical of plant origin to a medicine of clinical utility. In some cases the pharmaceutical product is still identical to and derived from the naturally occurring substance (eg, atropine), while, in others, considerable modification of the structure of the natural chemical was needed to produce a clinically useful agent (eg, lidocaine, verapamil). Each of the 17 sections is very short, with a full-page black-and-white engraving of the plant being discussed and up to an additional page-and-a-half
<b> <i>In Vivo</i> </b> Suppression of Hormone-Refractory Prostate Cancer Growth by Inositol Hexaphosphate
Authors: Rana P. Singh, Girish Sharma, G. U. Mallikarjuna, Sivanandhan Dhanalakshmi, Chapla Agarwal, Rajesh Agarwal
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Diet composition is an important etiologic factor in prostate cancer (PCA) growth and has significant impact on clinical PCA appearance. Because inositol hexaphosphate (IP6) is a dietary phytochemical present in cereals, soy, legumes, and fiber-rich foods, we evaluated efficacy of IP6 against PCA growth and associated molecular events. Experimental Design: DU145 cells were injected into nude mice, and animals were fed normal drinking water or 1 or 2% IP6 in drinking water for 12 weeks. Body weight, diet, water consumption, and tumor sizes were monitored. Tumors were immunohistochemically analyzed for proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase-mediated nick end labeling, and CD31. Tumor-secreted insulin-like growth factor binding protein (IGFBP)-3 and vascular endothelial growth factor (VEGF) were quantified in plasma by ELISA. Results: IP6 feeding resulted in suppression of hormone-refractory human prostate tumor growth without any adverse effect on body weight gain, diet, and water consumption during entire study. At the end of study, tumor growth inhibition by 1 and 2% IP6 feeding was 47 and 66% (P = 0.049–0.012) in terms of tumor volume/mouse and 40 and 66% (P = 0.08–0.003) in terms of tumor weight/mouse, respectively. Tumor xenografts from IP6-fed mice showed significantly (P &amp;lt; 0.001) decreased proliferating cell nuclear antigen-positive cells but increased apoptotic cells. Tumor-secreted IGFBP-3 levels were also increased up to 1.7-fold in IP6-fed groups. Additionally, IP6 strongly decreased tumor microvessel density and inhibited tumor-secreted VEGF levels. Conclusions: IP6 suppresses hormone-refractory PCA growth accompanied by inhibition of tumor cell proliferation and angiogenesis and increased apoptosis. IP6-caused increase in IGFBP-3 and decrease in VEGF might have a role in PCA growth control.
Swallowed button batteries: is there a consensus on management?
Authors: J G Studley, I P Linehan, A L Ogilvie, B L Dowling
Journal: Gut (1990)

The optimum management of ingested button batteries was ascertained by postal questionnaire sent to 608 members of the endoscopic and paediatric sections of the British Society of Gastroenterology. Some 312 returns were suitable for analysis: 36.2% of the respondents were not concerned about ingested button batteries and gave no treatment, 6.4% used medical treatment, 48.4% removed them under certain circumstances, and 9% did not know how to manage the problem. Emetics and H2 antagonists or antacids were often used for batteries in the oesophagus, stomach, and duodenum and laxatives were commonly prescribed for batteries in the small and large bowel. Of the 48.4% who felt batteries should be removed under certain circumstances, 78%, 72%, and 48% extracted them from the oesophagus, stomach, and duodenum respectively within 24 hours of ingestion. The main reason for operative removal from the small and large bowel was failure of the battery to progress. Current management is therefore variable. Heavy metal poisoning may be occurring more frequently than is suggested in the published reports.
Leptin signaling protects the gut from<i>Entamoeba histolytica</i>infection
Authors: Gayatri Vedantam, V. K. Viswanathan
Journal: Gut Microbes (2012)

The role of the adipose-derived hormone leptin, and leptin receptors, in signaling satiety to the central nervous system and regulating energy balance is well recognized. But leptin also acts on peripheral tissues such as skeletal muscles, adipose tissues, pancreas, liver, intestine and the immune system. The existence of different splice variants of leptin receptor and the numerous intracellular signaling pathways triggered by leptin make this a truly versatile system. Two recent studies explore the link between malnutrition, leptin signaling and susceptibility to amebic infection. These studies point to important and novel aspects of leptin signaling in maintaining gut homeostasis and warding off infections.
Endotoxin from <i>Haemophilus influenzae</i> enhances IgE‐mediated and non‐immunological histamine release
Authors: P. Clementsen, N. Milman, M. Kilian, A. Fomsgaard, L. Baek, S. Norn
Journal: Allergy (1990)

Haemophilus influenza and its extracellular produets (EP) ditl not release histamine from basophil leukocytes in cell suspensions from normal individuals, patients with chronic bronchitis or patients allergic to either house dust mite, grass pollen, eat dander or to their own bacteria. However, the EP was found to enhance their basophil histamine release. IgE‐mediated histamine release was examined by stimulation of the cells with anti‐IgE or the specific allergens, and non‐immunological histamine release by stimulating the cells with the calcium ionophore A23187 or Staphylococcus aureus. In all the experiments EP caused a significant increase in the histamine release. When H. influenzae endotoxins were removed from the EP, the potentiating effect of EP was completely abolished, whereas heating (80°C. 30 min) or treatment of EP with proteinase did not influence the potentiating effect. These results indicate that H. influenzae endotoxin potentiates histamine release caused by IgE‐mediated reactions or by non‐immunological mechanisms.
Feature extraction and feature interaction
Authors: Frank W. Ohl, Henning Scheich
Journal: Behavioral and Brain Sciences (1998)

The idea of the orderly output constraint is compared with recent findings about the representation of vowels in the auditory cortex of an animal model for human speech sound processing (Ohl &amp; Scheich 1997). The comparison allows a critical consideration of the idea of neuronal “feature extractors,” which is of relevance to the noninvariance problem in speech perception.
DYSPHAGIA ASSOCIATED WITH ANAEMIA
Authors: A. M. Jones, R. D. Owen
Journal: BMJ (1928)

<h3>Objective</h3> To investigate the prevalence of neutralizing antibodies (NAbs) against botulinum neurotoxin type A (BoNT/A) during long-term BoNT/A treatment in different neurologic indications. <h3>Methods</h3> In this monocentric, observational cross-sectional study, 596 outpatients treated with BoNT/A for different indications were tested for BoNT/A binding antibodies by ELISA. Positive samples were investigated for NAbs with the mouse hemidiaphragm test. The prevalence of NAbs was analyzed for different indications: facial hemispasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. Besides the rate of NAb-positive patients overall and per patient subgroup, a Kaplan-Meier analysis of the probability of remaining NAb negative with duration of treatment is provided, and a stepwise binary logistic regression analysis is performed to identify factors significantly contributing to the induction of NAbs. <h3>Results</h3> Overall, 83 of 596 patients (13.9%) had measurable NAbs. The probability of developing NAbs increased with the single and cumulative dose of treatment and was influenced by the BoNT/A formulation, while all other factors analyzed, including disease entity and treatment duration, had no additional influence. <h3>Conclusions</h3> We present the largest study to date of the prevalence of BoNT/A NAbs in a large unbiased cohort of patients including the relevant neurologic indications. Repeated injections of BoNT/A inevitably bear the risk of developing NAbs. However, in addition to avoiding booster injections and providing short intervals between injections, reducing the individual injected doses may diminish the risk of NAb induction independently of the indication for which BoNT/A is used.
Elemental carbon and PM(2.5 )levels in an urban community heavily impacted by truck traffic.
Authors: T Suvendrini Lena, Victor Ochieng, Majora Carter, José Holguín-Veras, Patrick L Kinney
Journal: Environmental Health Perspectives (2002)

Hunts Point, a 690-acre peninsula in the South Bronx, New York City, is a hub in the tristate (New York, New Jersey, and Connecticut) freight transportation system. This study was carried out in response to community concerns about potential health effects of exposure to diesel exhaust particulate (DEP). We measured particulate matter < 2.5 microm in aerodynamic diameter (PM(2.5)) and elemental carbon (EC) on sidewalks and tested whether spatial variations in concentrations were related to local truck traffic density. Ten-hour integrated air samples for EC and PM(2.5) were collected for 9 days over a 3-week period in the summer of 1999 at seven geographically distinct intersections. Simultaneous traffic counts were carried out for each sampling event. Traffic was classified into three classes: passenger cars, small trucks, and large trucks (diesel vehicles). Mean diesel vehicle volumes ranged from 9.3 to 276.5 vehicles/hr across sites. Mean EC concentrations by site ranged from 2.6 microg/m(3) at the control site to 7.3 microg/m(3) along a designated truck route. Linear regression of site-specific mean EC concentration on mean large truck counts predicted an increase of 1.69 microg/m(3) EC per 100 large trucks/hr (SE = 0.37; p = 0.01; R(2) = 0.84). Average PM(2.5) concentrations by site ranged 1.6-fold (19.0-29.9 microg/m(3)) and were more weakly associated with local traffic. Variations over time for PM(2.5 )were more pronounced, ranging almost 4-fold (8.9-34.4 microg/m(3)). These results show that airborne EC concentrations, an important component of DEP, are elevated in Hunts Point and that the impact varies across the community as a function of large truck traffic.
Foxp3+ Regulatory T Cells and Natural Killer Cells Distinctly Infiltrate Primary Tumors and Draining Lymph Nodes in Pulmonary Adenocarcinoma
Authors: Thomas Schneider, Silvia Kimpfler, Arne Warth, Philipp A. Schnabel, Hendrik Dienemann, Dirk Schadendorf, Hans Hoffmann, Viktor Umansky
Journal: Journal of Thoracic Oncology (2011)
Hospital admissions rise by 6% in England
Authors: C. White
Journal: BMJ (2010)

The number of people admitted to hospital for elective or emergency care rose by an average of 6% in England last year, an analysis shows.

This compares with an average annual growth of 4.6% in the preceding three years and is reflected in similar rises in Wales and Northern Ireland, sparking fears of a financial crisis for the NHS unless the trend can be reversed.

The analysis of hospital episode statistics by primary care trust, carried out by consultants CHKS, shows that in only a handful of trusts were admissions cut in 2008-9.

The best performing area was Cornwall and the Isles of Scilly, …
Trace Element Homeostasis During Continuous Sedation With Propofol Containing EDTA Versus Other Sedatives in Critically Ill Patients
Authors: T. L. Higgins, Michael Murray, Daniel H. Kett, Gerard Fulda, Katherine M. Kramer, David Gelmont, Harakh V. Dedhia, Howard Levy, Daniel Teres, Gary P. Zaloga, Haumei Ko, Karen A. Thompson
Journal: Intensive Care Medicine (2000)
Strategy for vaccination against hepatitis B in areas with high endemicity: focus on Korea.
Authors: Y O Ahn
Journal: Gut (1996)

Hepatitis B vaccination strategies may vary from country to country depending on hepatitis B virus (HBV) endemicity, predominant modes of infection, age of infection, and health care resources. In areas with high endemicity like Korea, transmission of virus from carrier mothers to infants during the perinatal period, and from other horizontal sources to infants and children, account for most cases of HBV infection. The consequences of HBV infection at an early age are serious, as more than 70% remain chronic carriers of the virus. These chronic carriers are the principal source of infection for other susceptible people, and are themselves at high risk of developing other serious diseases, such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. Theoretically, therefore, routine infant immunisation supplemented with prenatal screening of pregnant women for HBsAg or HBeAg and mass immunisation of children is the appropriate strategy for control of hepatitis B in these countries. To prevent primary liver cancer associated with HBV infection, however, immunisation of adults at high risk would also be prudent. Mandatory vaccination of all neonates is recommended in highly endemic areas, together with hepatitis B immune globulin in babies born to HBsAg carrier mothers.
WHAT CAN BE DONE FOR THE PREVENTION OF INSANITY BY THE TREATMENT OF INCIPIENT CASES IN GENERAL HOSPITALS, AND WHAT HAS BEEN DONE IN THE PAST
Authors: L. Vernon Briggs
Journal: American Journal of Psychiatry (1911)

Psychiatric wards in general hospitals would be the means of preventing insanity in a very large portion of cases because; 1st. The incipient case would have the advantage of immediate expert care by members of the hospital staff of physicians composed of every branch of medicine and surgery. 2d. He would have the advantage of a large hospital nursing staff in place of a few attendants. 3d. Suicide and attempts at suicide would often be prevented. 4th. The social considerations after recovery are most important to patients, 50 per cent of whom would be saved from being placed in an insane institution. 5th. An opportunity for clinical instruction to physicians and medical students which would result in the whole profession earlier recognizing incipient cases, an enormous gain to our profession and a greater gain to the public.
Active cascade testing for carriers of cystic fibrosis gene
Authors: M Super, M J Schwarz, G Malone, T Roberts, A Haworth, G Dermody
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b> : To examine the acceptability, practicability, efficiency, and application of active screening for carriers of the cystic fibrosis gene in the extended families of those in whom the disease is present (cascade screening). <b>Design</b> : Paediatricians and physicians provide details of their affected patients, pedigrees are drawn up, and relatives offered tests after initial contact by the affected nuclear families. Affected patients are genotyped in a laboratory with a special interest in the genetics of cystic fibrosis. <b>Setting</b> : North Western health region. <b>Subjects</b> : Relatives and partners of 607 people with cystic fibrosis. <b>Interventions</b> : Genetic counselling by letter for people found to be carriers; formal genetic counselling and when indicated arrangements for prenatal diagnosis for couples discovered to be carriers. Main outcome measures - Number of carrier couples detected; action in pregnancy of detected carrier couples; extent of the uptake of screening by relatives. <b>Results</b> : Of 1563 relatives or partners tested, 15 carrier couples were detected; of nine pregnancies undertaken by these 15, eight had prenatal tests and three terminated pregnancies. An average of 16 people per family have come forward for testing so far. <b>Conclusions</b> : Cascade screening for carriers of cystic fibrosis is well accepted by relatives, especially on the mother9s side of the family; it is 10 times more efficient in detecting carrier couples than unfocused screening. Detected carrier couples make practical use of the information in pregnancy. Active cascade screening for carriers is effective in cystic fibrosis and widespread application is recommended. These principles could be applied to other recessive disorders.
Abstract 3067: PIK3CA hotspot mutations are present at a relatively high frequency in CTCs of operable and metastatic breast cancer patients
Authors: Athina N. Markou, Sofia Farkona, Christina Schiza, Antonia Eftathiou, Nikolaos Malamos, Vassilis Georgoulias, Evi Lianidou
Journal: Cancer Research (2014)

Abstract Introduction: Molecular characterization of CTC is crucial for the investigation of molecular targeted therapies. PIK3CA somatic mutations play a crucial role in response to molecular targeted therapies. We detected PIK3CA mutations at a high frequency in CTC after developing and validating an ultra-sensitive methodology, based on a combination of allele-specific, asymmetric rapid PCR and melting analysis. Patient and Methods: After optimizing and validating our assay in terms of sensitivity, specificity and robustness, we detected PIK3CA hotspot mutations in EpCAM positive CTCs from 57 metastatic and 118 early breast cancer patients, 26 healthy individuals and 76 corresponding primary tumors. Rapid Real-PCR and melting were performed in triplicate for all samples in the LightScanner32 (Idaho USA), in the presence of LC-Green Plus saturating dye. Results: The assay could detect 0.05% of mutated dsDNA in the presence of 99.95% wtDNA for both exons and was highly specific (0/26 healthy). We identified PIK3CA mutations in EpCAM positive CTC in 20/57(35.1%) metastatic and in 23/118(19.5%) operable breast cancer patients. In corresponding primary tumors, 45/76(59.2%) samples were positive. Patients with verified metastasis carrying PIK3CA mutations on CTC had significant shorter OS than those without. Conclusions: We report for the first time that PIK3CA hotspot mutations are present at a relatively high frequency in CTC both in metastatic and operable breast cancer. The presence of PIK3CA mutations in CTC is associated with worse survival in patients with verified metastasis. Evaluation of PIK3CA mutational status on CTCs is a strategy with potential clinical application. Citation Format: Athina N. Markou, Sofia Farkona, Christina Schiza, Antonia Eftathiou, Nikolaos Malamos, Vassilis Georgoulias, Evi Lianidou. PIK3CA hotspot mutations are present at a relatively high frequency in CTCs of operable and metastatic breast cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3067. doi:10.1158/1538-7445.AM2014-3067
Hepatocyte signaling through CXC chemokine receptor-2 is detrimental to liver recovery after ischemia/reperfusion in mice
Authors: Satoshi Kuboki, Thomas Shin, Nadine Huber, Thorsten Eismann, Elizabeth Galloway, Rebecca Schuster, John Blanchard, Michael J. Edwards, Alex B. Lentsch
Journal: Hepatology (2008)

CXC chemokines and their receptor, CXC chemokine receptor-2 (CXCR2), are important components of the hepatic inflammatory response to ischemia/reperfusion (I/R). However, direct effects of CXC chemokines on hepatocytes during this response have not been studied. Wild-type and CXCR2−/− mice were subjected to 90 minutes of partial hepatic ischemia followed by up to 96 hours of reperfusion. CXCR2−/− mice had significantly less liver injury at all reperfusion times compared with wild-type mice. Early neutrophil recruitment (12 hours) was diminished in CXCR2−/− mice, but within 24 hours it was the same as that of wild-type mice. Hepatocyte proliferation and regeneration was accelerated in CXCR2−/− mice compared with wild-type mice. These effects were associated with increased activation of nuclear factor κB and signal transducers and activators of transcription-3, despite there being no difference in the expression of proliferative factors such as tumor necrosis factor α, interleukin-6, and hepatocyte growth factor. To establish whether the accelerated proliferation and regeneration observed in CXCR2−/− mice was due to effects on hepatocytes rather than just a generalized decrease in acute inflammatory injury, mice were treated with the CXCR2 antagonist, SB225002, after neutrophil recruitment and injury were maximal (24 hours after reperfusion). SB225002 treatment increased hepatocyte proliferation and regeneration in a manner identical to that observed in CXCR2−/− mice. Treatment of primary wild-type hepatocytes with macrophage inflammatory protein-2 revealed that low concentrations protected against cell death, whereas high concentrations induced cell death. These effects were absent in hepatocytes from CXCR2−/− mice. Conclusion: Our data suggest that hepatocyte CXCR2 regulates proliferation and regeneration after I/R injury and reveal important differences in the role of this receptor in liver regeneration and repair induced under different conditions that may be related to ligand concentration. (HEPATOLOGY 2008.)