tbuckley/cabot-search huggingface dataset:
Cardiac Voltage-Gated Sodium Channel Na <sub>v</sub> 1.5 Is Regulated by Nedd4-2 Mediated Ubiquitination
Authors: Miguel X. van Bemmelen, Jean-Sébastien Rougier, Bruno Gavillet, Florine Apothéloz, Dorothée Daidié, Michihiro Tateyama, Ilaria Rivolta, Marc A. Thomas, Robert S. Kass, Olivier Staub, Hugues Abriel
Journal: Circulation Research (2004)

Na v 1.5, the cardiac isoform of the voltage-gated Na + channel, is critical to heart excitability and conduction. However, the mechanisms regulating its expression at the cell membrane are poorly understood. The Na v 1.5 C-terminus contains a PY-motif (xPPxY) that is known to act as binding site for Nedd4/Nedd4-like ubiquitin-protein ligases. Because Nedd4-2 is well expressed in the heart, we investigated its role in the ubiquitination and regulation of Na v 1.5. Yeast two-hybrid and GST-pulldown experiments revealed an interaction between Na v 1.5 C-terminus and Nedd4-2, which was abrogated by mutating the essential tyrosine of the PY-motif. Ubiquitination of Na v 1.5 was detected in both transfected HEK cells and heart extracts. Furthermore, Nedd4-2–dependent ubiquitination of Na v 1.5 was observed. To test for a functional role of Nedd4-2, patch-clamp experiments were performed on HEK cells expressing wild-type and mutant forms of both Na v 1.5 and Nedd4-2. Na v 1.5 current density was decreased by 65% upon Nedd4-2 cotransfection, whereas the PY-motif mutant channels were not affected. In contrast, a catalytically inactive Nedd4-2 had no effect, indicating that ubiquitination mediates this downregulation. However, Nedd4-2 did not alter the whole-cell or the single channel biophysical properties of Na v 1.5. Consistent with the functional findings, localization at the cell periphery of Na v 1.5-YFP fusion proteins was reduced upon Nedd4-2 coexpression. The Nedd4-1 isoform did not regulate Na v 1.5, suggesting that Nedd4-2 is a specific regulator of Na v 1.5. These results demonstrate that Na v 1.5 can be ubiquitinated in heart tissues and that the ubiquitin-protein ligase Nedd4-2 acts on Na v 1.5 by decreasing the channel density at the cell surface.
Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris
Authors: P. Papageorgiou, A. Katsambas, A. Chu
Journal: British Journal of Dermatology (2000)

Journal Article Phototherapy with blue (415 nm) and red (660 nm) light in the treatment of acne vulgaris Get access P. Papageorgiou, P. Papageorgiou Unit of Dermatology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. Katsambas, A. Katsambas Adreas Sygros Hospital, Athens, Greece Search for other works by this author on: Oxford Academic Google Scholar A. Chu A. Chu Unit of Dermatology, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, DuCane Road, London W12 0NN, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 142, Issue 5, 1 May 2000, Pages 973–978, https://doi.org/10.1046/j.1365-2133.2000.03481.x Published: 01 May 2000
Mania, dementia and melancholia in the 1870s: admissions to a Cornwall asylum
Authors: S. A Hill, R. Laugharne
Journal: Journal of the Royal Society of Medicine (2003)

In the 1870s St Lawrence's Hospital in Bodmin, Cornwall, had been running for 50 years, one of sixteen county asylums set up between 1811 and 1842. By examining 511 admissions between 1870 and 1875 to this typical Victorian asylum we hoped to shed light on this mid-point of the asylum era. The 511 patients were all classified as 'paupers', whose admissions were publicly funded. A few privately funded patients were admitted during this period but are not included.

Asylum populations rose greatly through the 19th century. Whether this rise was mainly due to an increase in psychotic illness or to a decrease in tolerance of the mentally ill in the community is unclear. Many patients were admitted under the Poor Law and Lunacy Acts. After amending acts of 1853, the parish medical officer was required to visit all paupers in his areas four times a year. He was expected to notify the guardians or the overseers of those who seemed in need of mental treatment.1 If any were thought to need treatment in the asylum, admission was certified by the medical officer and the local justice of the peace.
Inter- and Intraspecies Metabolite Exchange Promotes Virulence of Antibiotic-Resistant Staphylococcus aureus
Authors: Neal D. Hammer, James E. Cassat, Michael J. Noto, Lisa J. Lojek, Ashley D. Chadha, Jonathan E. Schmitz, C. Buddy Creech, Eric P. Skaar
Journal: Cell Host & Microbe (2014)
HIV and pregnancy
Authors: Glenda E Gray, James A McIntyre
Journal: BMJ (2007)

The management of HIV infection during pregnancy is complex, and the scenario box on this page illustrates the complexities involved. In 2005, UNAIDS (the Joint United Nations Programme on HIV/AIDS) estimated that 38.6 million people had HIV, of whom 17.3 million were women (with most being in their reproductive years). At least 3.28 million pregnant women infected with HIV are estimated to give birth each year, with more than 75% of these in sub-Saharan Africa; this is where most of the annual 700 000 new infections of HIV in children occur. #### SCENARIO A 27 year old woman is referred to the antenatal clinic at 16 weeks of pregnancy. This is her second pregnancy—her first child, delivered by caesarean section, is now 8 years old. The mother was diagnosed with HIV four years ago when she developed herpes zoster. She has been taking zidovudine, lamivudine, and nevirapine for four weeks through an antiretroviral treatment access programme. At the time of starting treatment, her CD4 count was 124×106 cells/l, her viral load 50 000 copies/ml, and her haemoglobin 104 g/l. She had received a negative screening result for tuberculosis and was receiving daily co-trimoxazole prophylaxis for preventing opportunistic infections. At the 16 week visit she was found to have a haemoglobin concentration of 87 g/l. She is from an African community and has not disclosed her HIV status to her family; she is concerned about the possible stigma associated with not breast feeding her infant. ##### Comments
Platelet Glycoprotein Ibα Is a Counterreceptor for the Leukocyte Integrin Mac-1 (Cd11b/Cd18)
Authors: Daniel I. Simon, Zhiping Chen, Hui Xu, Chester Q. Li, Jing-fei Dong, Larry V. McIntire, Christie M. Ballantyne, Li Zhang, Mark I. Furman, Michael C. Berndt, José A. López
Journal: The Journal of Experimental Medicine (2000)

The firm adhesion and transplatelet migration of leukocytes on vascular thrombus are both dependent on the interaction of the leukocyte integrin, Mac-1, and a heretofore unknown platelet counterreceptor. Here, we identify the platelet counterreceptor as glycoprotein (GP) Ibα, a component of the GP Ib-IX-V complex, the platelet von Willebrand factor (vWf) receptor. THP-1 monocytic cells and transfected cells that express Mac-1 adhered to GP Ibα–coated wells. Inhibition studies with monoclonal antibodies or receptor ligands showed that the interaction involves the Mac-1 I domain (homologous to the vWf A1 domain), and the GP Ibα leucine-rich repeat and COOH-terminal flanking regions. The specificity of the interaction was confirmed by the finding that neutrophils from wild-type mice, but not from Mac-1–deficient mice, bound to purified GP Ibα and to adherent platelets, the latter adhesion being inhibited by pretreatment of the platelets with mocarhagin, a protease that specifically cleaves GP Ibα. Finally, immobilized GP Ibα supported the rolling and firm adhesion of THP-1 cells under conditions of flow. These observations provide a molecular target for disrupting leukocyte–platelet complexes that promote vascular inflammation in thrombosis, atherosclerosis, and angioplasty-related restenosis.
Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma: Recursive Partitioning Analysis of the EORTC 26981/22981-NCIC CE3 Phase III Randomized Trial
Authors: René-Olivier Mirimanoff, Thierry Gorlia, Warren Mason, Martin J. Van den Bent, Rolf-Dieter Kortmann, Barbara Fisher, Michele Reni, Alba A. Brandes, Jüergen Curschmann, Salvador Villa, Gregory Cairncross, Anouk Allgeier, Denis Lacombe, Roger Stupp
Journal: Journal of Clinical Oncology (2006)

The European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada trial on temozolomide (TMZ) and radiotherapy (RT) in glioblastoma (GBM) has demonstrated that the combination of TMZ and RT conferred a significant and meaningful survival advantage compared with RT alone. We evaluated in this trial whether the recursive partitioning analysis (RPA) retains its overall prognostic value and what the benefit of the combined modality is in each RPA class.Five hundred seventy-three patients with newly diagnosed GBM were randomly assigned to standard postoperative RT or to the same RT with concomitant TMZ followed by adjuvant TMZ. The primary end point was overall survival. The European Organisation for Research and Treatment of Cancer RPA used accounts for age, WHO performance status, extent of surgery, and the Mini-Mental Status Examination.Overall survival was statistically different among RPA classes III, IV, and V, with median survival times of 17, 15, and 10 months, respectively, and 2-year survival rates of 32%, 19%, and 11%, respectively (P < .0001). Survival with combined TMZ/RT was higher in RPA class III, with 21 months median survival time and a 43% 2-year survival rate, versus 15 months and 20% for RT alone (P = .006). In RPA class IV, the survival advantage remained significant, with median survival times of 16 v 13 months, respectively, and 2-year survival rates of 28% v 11%, respectively (P = .0001). In RPA class V, however, the survival advantage of RT/TMZ was of borderline significance (P = .054).RPA retains its prognostic significance overall as well as in patients receiving RT with or without TMZ for newly diagnosed GBM, particularly in classes III and IV.
A phase I study of OSI-211 and cisplatin as intravenous infusions given on days 1, 2 and 3 every 3 weeks in patients with solid cancers
Authors: M.J. MacKenzie, H.W. Hirte, L.L. Siu, K. Gelmon, M. Ptaszynski, B. Fisher, E. Eisenhauer
Journal: Annals of Oncology (2004)
Lung volume: a principle determinant of airway smooth muscle function
Authors: C.G. Irvin
Journal: European Respiratory Journal (2003)

A total of 104 eyes and 43 resected corneal discs from patients with failed intraocular lens implants (IOL) received over a period of 35 years were subjected to histopathological analysis. Eyes collected at necropsy from 18 people with clinically successful implants were also examined. Corneal decompensation leading to bullous keratopathy was the most frequent reason for failure, followed by glaucoma and intraocular inflammation. Of 18 cases in which inflammation was the principal clinical cause of failure 12 presented as infectious endophthalmitis, but minor degrees of sterile uveitis were fairly common. Retinal detachment was seen in seven cases. The interval between IOL implantation and the onset of serious complications varied from one month to 29 years, indicating that the presence of prosthesis will always entail a latent risk of an adverse tissue response, albeit slight.
Effectiveness of Adding Montelukast to Low Dose Inhaled Corticosteroids in Patients with Uncontrolled Asthma and Allergic Rhinitis
Authors: C KOCH, R MCIVOR, S COYLE, N HARVEY, S FOUCART, F PSARADELLIS, J SAMPALIS, J FITZGERALD
Journal: Journal of Allergy and Clinical Immunology (2008)
Aspirin Use and Counseling About Aspirin Among Patients With Diabetes
Authors: Sarah L. Krein, Sandeep Vijan, Leonard M. Pogach, Mary M. Hogan, Eve A. Kerr
Journal: Diabetes Care (2002)

Despite being a safe, effective therapy for lowering cardiovascular risk, only 20% of diabetic patients were using aspirin in the early 1990s. This study examines current physician practices and the use of aspirin therapy by individuals with diabetes.A random sample of diabetic patients receiving care in the Department of Veterans Affairs health care system were surveyed during January-March 2000. The association between aspirin counseling, aspirin use, and reported coronary vascular disease (CVD) and classical CVD risk factors were examined using logistic regression. The effect of increasing aspirin use on risk of myocardial infarction (MI) and cardiovascular mortality was demonstrated by simulation.Seventy-one percent of respondents reported being counseled about aspirin use, and 66% were taking daily aspirin. Individuals with known CVD were more likely to be counseled (odds ratio [OR] 4.9, 95% CI 2.9-8.1) and to use aspirin (2.1, 1.2-3.7). The factor most strongly associated with aspirin use was having been counseled about aspirin therapy by a doctor. We estimate that for this population, increasing daily aspirin use to 90% could prevent an additional 11,000 MIs and potentially save >8,000 lives.Compared with previous reports, a substantial proportion of these diabetic patients have been counseled about and use aspirin. Most clinicians recognize aspirin as an important treatment for patients with preexisting coronary disease. However, since diabetes is now considered a CVD equivalent, it is imperative that clinicians include counseling about aspirin therapy as a care priority for all their diabetic patients, as this simple intervention may prevent many cardiovascular events and deaths.
A tale of one city.
Authors: C. M. De Wind
Journal: BMJ (1992)

A report from Kampala, Uganda, compares the situation in 1991 to the state of chaos 10 years earlier when the regime of Idi Amin had been overthrown by Milton Obote's soldiers with the help of Tanzanian troops. Soldiers went on looting sprees, and 1 victim of their marauding became a 12-year old boy who got shot for refusing to part with his bike. In contrast, in 1991 things were much more peaceful; however, the AIDS epidemic was the new threat. The government radio transmits hourly warnings on HIV. Since President Museveni came to power, economy and security have improved radically. Shops and markets are open until late at night; public transport is reliable, and small scale industry flourished. There would be optimism about the future, if AIDS was not here. There is no doubt that the economy will soon be affected. According to the Kampala blood bank, 40% of the healthy population is already seropositive. In the hospitals the majority of admissions suffer from AIDS with diarrhea and an itching dermatitis; there is more cancer of the cervix and lymphoma; appendicitis is on the increase; and tuberculous lymph nodes are now quite common. Many of these patients have clinical AIDS. The government is frank about the situation and is active in preventive measures and education. Private charities and foreign aid organizations contribute. But the epidemic is so overwhelming, that some Western organizations might soon lose interest owning to meager returns on their efforts. A 6-year-old boy has grossly swollen lymph nodes around his neck, both parotids are painfully swollen, pus pours from the ears. A nonspecific cough and mild diarrhea are also present with an itching and sore herpes zoster on his left chest. the mother is frightened of losing him, and demurs at the hint of AIDS, since for her, AIDS means sexual promiscuity.
Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans
Authors: Shinobu Saijo, Noriyuki Fujikado, Takahisa Furuta, Soo-hyun Chung, Hayato Kotaki, Keisuke Seki, Katsuko Sudo, Shizuo Akira, Yoshiyuki Adachi, Naohito Ohno, Takeshi Kinjo, Kiwamu Nakamura, Kazuyoshi Kawakami, Yoichiro Iwakura
Journal: Nature Immunology (2006)
Metformin decreases hepatocellular carcinoma risk in a dose-dependent manner: population-based and in vitro studies
Authors: Hsiao-Ping Chen, Jeng-Jer Shieh, Chia-Che Chang, Tzu-Ting Chen, Jaw-Town Lin, Ming-Shiang Wu, Jeng-Horng Lin, Chun-Ying Wu
Journal: Gut (2012)

Type 2 diabetes mellitus is associated with a higher risk of hepatocellular carcinoma (HCC), which is attenuated by the use of metformin. However, there are no studies addressing the effect of metformin on hepatocarcinoma cells from the antitumoural perspective.In the nationwide case-control study, the authors recruited 97,430 HCC patients and 19,860 age-, gender- and physician visit date-matched controls. The chemopreventive effects of metformin were examined by multivariate analysis and stratified analysis. The in vitro effects of metformin on cell proliferation and cell cycle were studied in HepG2 and Hep3B hepatoma cell lines.The OR of diabetes in HCC patients was 2.29 (95% CI 2.25 to 2.35, p<0.001). Each incremental year increase in metformin use resulted in 7% reduction in the risk of HCC in diabetic patients (adjusted OR=0.93, 95% CI 0.91 to 0.94, p<0.0001). In the multivariate stratified analysis, metformin use was associated with a reduced risk of HCC in diabetic patients in nearly all subgroups. Cell line studies showed that metformin inhibits hepatocyte proliferation and induces cell cycle arrest at G0/G1 phase via AMP-activated protein kinase and its upstream kinase LKB1 to upregulate p21/Cip1 and p27/Kip1 and downregulate cyclin D1 in a dose-dependent manner, but independent of p53. Combined treatment of oral metformin with doxorubicin functioned more efficiently than either agent alone, in vivo.Use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner, via inhibition of hepatoma cells proliferation and induction of cell cycle arrest at G0/G1 phase.
Sentinel Lymph Node Biopsy Accurately Stages the Regional Lymph Nodes for T1-T2 Oral Squamous Cell Carcinomas: Results of a Prospective Multi-Institutional Trial
Authors: Francisco J. Civantos, Robert P. Zitsch, David E. Schuller, Amit Agrawal, Russell B. Smith, Richard Nason, Guy Petruzelli, Christine G. Gourin, Richard J. Wong, Robert L. Ferris, Adel El Naggar, John A. Ridge, Randal C. Paniello, Kouros Owzar, Linda McCall, Douglas B. Chepeha, Wendell G. Yarbrough, Jeffrey N. Myers
Journal: Journal of Clinical Oncology (2010)

The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection.This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with (99m)Tc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB.In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%.For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%).
Bronchoscopy with transbronchial biopsies: measurement of bleeding volume and evaluation of the predictive value of coagulation tests
Authors: O Bjørtuft, F Brosstad, J Boe
Journal: European Respiratory Journal (1998)

The objectives of this study were to measure the bleeding volume associated with fibreoptic bronchoscopy with transbronchial biopsies (TBB), to correlate it with coagulation tests and to compare bleeding volume in patients with and without lung transplant. A total of 104 consecutive TBB in 51 different patients was evaluated prospectively. Before each procedure, haemoglobin, blood platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT) and bleeding time were measured. During the procedure, lavage fluid and blood were collected by suction. The haemoglobin concentration of the mixture was measured and bleeding volume was calculated. Clinically significant bleeding was arbitrarily defined as &gt;20 mL blood present in lavage fluid. The mean+/-SD bleeding volume was 7+/-10 mL with no statistically significant difference between transplanted and nontransplanted patients. In eight procedures (7.7%) the bleeding volume was &gt;20 mL (range 22-61 mL). Prebiopsy values for blood platelet counts, PT and aPTT did not predict a bleeding tendency in any of the procedures in which significant bleeding occurred. No correlation was found between bleeding time and bleeding volume in the 17 procedures performed in patients with a prolonged bleeding time (&gt; or =10 min). The bleeding associated with transbronchial biopsies was usually minor and quantitatively similar in patients with or without lung transplant. Coagulation tests could not predict clinically significant bleeding, which may occur in patients with normal coagulation test results.
cGMP-Dependent Protein Kinases and cGMP Phosphodiesterases in Nitric Oxide and cGMP Action
Authors: Sharron H. Francis, Jennifer L. Busch, Jackie D. Corbin
Journal: Pharmacological Reviews (2010)

To date, studies suggest that biological signaling by nitric oxide (NO) is primarily mediated by cGMP, which is synthesized by NO-activated guanylyl cyclases and broken down by cyclic nucleotide phosphodiesterases (PDEs). Effects of cGMP occur through three main groups of cellular targets: cGMP-dependent protein kinases (PKGs), cGMP-gated cation channels, and PDEs. cGMP binding activates PKG, which phosphorylates serines and threonines on many cellular proteins, frequently resulting in changes in activity or function, subcellular localization, or regulatory features. The proteins that are so modified by PKG commonly regulate calcium homeostasis, calcium sensitivity of cellular proteins, platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes. Current therapies that have successfully targeted the NO-signaling pathway include nitrovasodilators (nitroglycerin), PDE5 inhibitors [sildenafil (Viagra and Revatio), vardenafil (Levitra), and tadalafil (Cialis and Adcirca)] for treatment of a number of vascular diseases including angina pectoris, erectile dysfunction, and pulmonary hypertension; the PDE3 inhibitors [cilostazol (Pletal) and milrinone (Primacor)] are used for treatment of intermittent claudication and acute heart failure, respectively. Potential for use of these medications in the treatment of other maladies continues to emerge.