tbuckley/cabot-search huggingface dataset:
Inositol 1, 4, 5-Trisphosphate Receptors and Human Left Ventricular Myocytes
Authors: Sergio Signore, Andrea Sorrentino, João Ferreira-Martins, Ramaswamy Kannappan, Mehrdad Shafaie, Fabio Del Ben, Kazuya Isobe, Christian Arranto, Ewa Wybieralska, Andrew Webster, Fumihiro Sanada, Barbara Ogórek, Hanqiao Zheng, Xiaoxia Liu, Federica del Monte, David A. D’Alessandro, Oriyanhan Wunimenghe, Robert E. Michler, Toru Hosoda, Polina Goichberg, Annarosa Leri, Jan Kajstura, Piero Anversa, Marcello Rota
Journal: Circulation (2013)

Background— Little is known about the function of inositol 1,4,5-trisphosphate receptors (IP3Rs) in the adult heart experimentally. Moreover, whether these Ca 2+ release channels are present and play a critical role in human cardiomyocytes remains to be defined. IP3Rs may be activated after Gαq-protein–coupled receptor stimulation, affecting Ca 2+ cycling, enhancing myocyte performance, and potentially favoring an increase in the incidence of arrhythmias. Methods and Results— IP3R function was determined in human left ventricular myocytes, and this analysis was integrated with assays in mouse myocytes to identify the mechanisms by which IP3Rs influence the electric and mechanical properties of the myocardium. We report that IP3Rs are expressed and operative in human left ventricular myocytes. After Gαq-protein–coupled receptor activation, Ca 2+ mobilized from the sarcoplasmic reticulum via IP3Rs contributes to the decrease in resting membrane potential, prolongation of the action potential, and occurrence of early afterdepolarizations. Ca 2+ transient amplitude and cell shortening are enhanced, and extrasystolic and dysregulated Ca 2+ elevations and contractions become apparent. These alterations in the electromechanical behavior of human cardiomyocytes are coupled with increased isometric twitch of the myocardium and arrhythmic events, suggesting that Gαq-protein–coupled receptor activation provides inotropic reserve, which is hampered by electric instability and contractile abnormalities. Additionally, our findings support the notion that increases in Ca 2+ load by IP3Rs promote Ca 2+ extrusion by forward-mode Na + /Ca 2+ exchange, an important mechanism of arrhythmic events. Conclusions— The Gαq-protein/coupled receptor/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias.
Diagnosis of tinea pedis by the Dermatophyte Test Strip
Authors: Y. Tsunemi, K. Takehara, Y. Miura, G. Nakagami, H. Sanada, M. Kawashima
Journal: British Journal of Dermatology (2015)

Funding sources: This survey was supported, in parts, by grants from the nonprofit organization Health Institute for Skin Research; Daiwa Securities Health Foundation; Chiyoda Mutual Life Foundation; St. Luke's Life Science Institute; and the Japan Foundation for Aging and Health. Conflicts of interest: none declared. Dear Editor, Tinea pedis is highly prevalent and is often seen in daily practice.1 However, it is difficult to diagnose tinea pedis visually because there are many similar diseases.2 3 Thus, a definitive diagnosis by mycological examination is necessary before the initiation of treatment for tinea pedis.2 3 Direct microscopy and fungal culture are used as test methods.2 3 4 However, direct microscopy has the disadvantage that the detection sensitivity is affected by the skill of the person who performs the test,4 while fungal culture takes 2–3 weeks for the identification of pathogenic fungi and has a low identification rate.4 The Dermatophyte Test Strip (JNC Corp., Tokyo, Japan) is a recently developed product that permits detection of mycotic antigens by immunochromatography in samples such as scales and nails.5 This test strip is likely to be useful clinically because it does not require special devices or skills, and can detect dermatophyte antigens from clinical samples in a short period of time. Compared with the standard method of direct microscopy, we have previously shown that the Dermatophyte Test Strip has sufficient sensitivity and specificity for the diagnosis of tinea unguium.5 There have also been some preliminary reports on the diagnosis of tinea pedis using the Dermatophyte Test Strip.6 7 8
Rifampin and Pyrazinamide vs Isoniazid for Prevention of Tuberculosis in HIV-Infected Persons&lt;SUBTITLE&gt;An International Randomized Trial&lt;/SUBTITLE&gt;
Authors: Fred Gordin
Journal: JAMA (2000)

5][6] The American Thoracic Society and the Centers for Disease Control and Prevention (CDC) currently recommend 6 months or longer of isoniazid daily for tuberculosis preventive therapy. 7Difficulties with isoniazid preventive therapy, however, in-clude poor adherence, 8 hepatotoxicity, 9 and organisms with isoniazid resistance, both in the United States and globally. 10,11Given these limitations, the development of alternative, shorter regi-
Effective treatment of psoriasis with etanercept is linked to suppression of IL-17 signaling, not immediate response TNF genes
Authors: Lisa C. Zaba, Mayte Suárez-Fariñas, Judilyn Fuentes-Duculan, Kristine E. Nograles, Emma Guttman-Yassky, Irma Cardinale, Michelle A. Lowes, James G. Krueger
Journal: Journal of Allergy and Clinical Immunology (2009)
Meningitis From a Pneumococcus Moderately Resistant to Penicillin
Authors: J. Carlton Gartner
Journal: JAMA (1979)

Strains of pneumococci moderately resistant to penicillin were recovered from three patients at the Children's Hospital of Pittsburgh during 1978. One of these children had meningitis and showed signs of early relapse despite high doses of penicillin G potassium. Routine screening of pneumococci for penicillin resistance is recommended. (<i>JAMA</i>241:1707-1709, 1979)
Lack of involvement of type 7 phosphodiesterase in an experimental model of asthma
Authors: E. Chevalier, V. Lagente, M. Dupont, H. Fargeau, X. Palazzi, V. Richard, M. Dassaud, M. Fric, M. Coupe, C. Carré, S. Leduc, P. Bernardelli, F. Vergne, P. Berna, C.P. Bertrand
Journal: European Respiratory Journal (2011)

Type 7 phosphodiesterases (PDE7) are responsible for the decrease of intracellular cyclic AMP (cAMP) in many cells involved in allergic asthma by suppressing their potential to respond to many activating stimuli. The elevation of intracellular cAMP has been associated with immunosuppressive and anti-inflammatory activities and represents a potential treatment of asthma. Our aim was to evaluate the impact of the deletion of the murine phosphodiesterase (PDE)7B gene and then to evaluate the efficacy of a newly described selective PDE7A and -B inhibitor on an ovalbumin (OVA)-induced airway inflammation and airway hyperreactivity (AHR) model in mice. Inflammation was determined 72 h after single OVA challenge or 24 h after multiple challenges by the relative cell influx and cytokine content in bronchoalveolar lavage fluid. AHR and immunoglobulin E levels in serum were determined after multiple challenges. For the first time, we have demonstrated that the deletion of the PDE7B gene or the pharmacological inhibition of PDE7A and -B had no effect on all the parameters looked at in this model. These results highlight the absence of any implication of the PDE7 enzyme in our model.
The Routine Guaiac Stool Test
Authors: C. Lawrence Holt
Journal: New England Journal of Medicine (1952)

AN EVALUATION of the importance of routine stool testing in the internist's office for occult blood was made by reviewing 1600 consecutive office records of new patients.Stool specimens brought to the office in a container proved more satisfactory than those obtained on the gloved finger at routine rectal examination. A light-green discoloration of the stool and chemical mixture on a white porcelain-tile plate was graded as + and was considered of no importance. A bluish-green color developing slowly (over a period of more than one minute) was graded as ++ and was classed as equivocal. A definitely blue reaction, . . .
A critical role for IRAK4 kinase activity in Toll-like receptor–mediated innate immunity
Authors: Tae Whan Kim, Kirk Staschke, Katarzyna Bulek, Jianhong Yao, Kristi Peters, Keun-Hee Oh, Yvonne Vandenburg, Hui Xiao, Wen Qian, Tom Hamilton, Booki Min, Ganes Sen, Raymond Gilmour, Xiaoxia Li
Journal: The Journal of Experimental Medicine (2007)

IRAK4 is a member of IL-1 receptor (IL-1R)–associated kinase (IRAK) family and has been shown to play an essential role in Toll-like receptor (TLR)–mediated signaling. We recently generated IRAK4 kinase-inactive knock-in mice to examine the role of kinase activity of IRAK4 in TLR-mediated signaling pathways. The IRAK4 kinase–inactive knock-in mice were completely resistant to lipopolysaccharide (LPS)- and CpG-induced shock, due to impaired TLR-mediated induction of proinflammatory cytokines and chemokines. Although inactivation of IRAK4 kinase activity did not affect the levels of TLR/IL-1R–mediated nuclear factor κB activation, a reduction of LPS-, R848-, and IL-1–mediated mRNA stability contributed to the reduced cytokine and chemokine production in bone marrow–derived macrophages from IRAK4 kinase–inactive knock-in mice. Both TLR7- and TLR9-mediated type I interferon production was abolished in plasmacytoid dendritic cells isolated from IRAK4 knock-in mice. In addition, influenza virus–induced production of interferons in plasmacytoid DCs was also dependent on IRAK4 kinase activity. Collectively, our results indicate that IRAK4 kinase activity plays a critical role in TLR-dependent immune responses.
A transcriptional network associated with natural variation in Drosophila aggressive behavior
Authors: Alexis C Edwards, Julien F Ayroles, Eric A Stone, Mary Anna Carbone, Richard F Lyman, Trudy FC Mackay
Journal: Genome biology (2009)

Aggressive behavior is an important component of fitness in most animals. Aggressive behavior is genetically complex, with natural variation attributable to multiple segregating loci with allelic effects that are sensitive to the physical and social environment. However, we know little about the genes and genetic networks affecting natural variation in aggressive behavior. Populations of Drosophila melanogaster harbor quantitative genetic variation in aggressive behavior, providing an excellent model system for dissecting the genetic basis of naturally occurring variation in aggression.Correlating variation in transcript abundance with variation in complex trait phenotypes is a rapid method for identifying candidate genes. We quantified aggressive behavior in 40 wild-derived inbred lines of D. melanogaster and performed a genome-wide association screen for quantitative trait transcripts and single feature polymorphisms affecting aggression. We identified 266 novel candidate genes associated with aggressive behavior, many of which have pleiotropic effects on metabolism, development, and/or other behavioral traits. We performed behavioral tests of mutations in 12 of these candidate genes, and show that nine indeed affected aggressive behavior. We used the genetic correlations among the quantitative trait transcripts to derive a transcriptional genetic network associated with natural variation in aggressive behavior. The network consists of nine modules of correlated transcripts that are enriched for genes affecting common functions, tissue-specific expression patterns, and/or DNA sequence motifs.Correlations among genetically variable transcripts that are associated with genetic variation in organismal behavior establish a foundation for understanding natural variation for complex behaviors in terms of networks of interacting genes.
Corrigendum to “Vascular remodeling and antitumoral effects of mTOR inhibition in a rat model of hepatocellular carcinoma” [J Hepatol 46 (2007) 840–848]
Authors: David Semela, Anne-Christine Piguet, Mirjam Kolev, Karin Schmitter, Ruslan Hlushchuk, Valentin Djonov, Christoforos Stoupis, Jean-François Dufour
Journal: Journal of Hepatology (2008)
A high incidence of MSH6 mutations in Amsterdam criteria II-negative families tested in a diagnostic setting
Authors: D Ramsoekh, A Wagner, M E van Leerdam, W N M Dinjens, E W Steyerberg, D J J Halley, E J Kuipers, D Dooijes
Journal: Gut (2008)

In Lynch syndrome, the clinical phenotype in MSH6 mutation families differs from that in MLH1 and MSH2 families. Therefore, MSH6 mutation families are less likely to fulfil diagnostic criteria such as the Amsterdam II criteria (AC II) and the revised Bethesda guidelines (rBG), and will be underdiagnosed. The aim of the present study was to evaluate the contribution of MSH6 gene mutations in families that were analysed for Lynch syndrome in a diagnostic setting.Families that had molecular analysis for Lynch syndrome were included in this study. Complete molecular screening of the MLH1, MSH2 and MSH6 genes was performed in all families. Microsatellite instability (MSI) and immunohistochemical (IHC) analysis was performed in almost all families. Clinical data were collected from medical records and family pedigrees.A total of 108 families were included. MSI and IHC analysis was performed in 97 families, and in 40 an MSI-high phenotype with absent protein expression was found. Germline mutation analysis detected mutations in 23 families (7 MLH1, 4 MSH2 and 12 MSH6). The majority of MSH6 families were AC II negative, but fulfilled the rBG.There is a high incidence of MSH6 mutations in families tested for Lynch syndrome in a diagnostic setting. Many of these families remain underdiagnosed using the AC II. The rBG are more useful to select these families for further analysis. However, to optimise the detection of MSH6 families, MSI and IHC analysis should also be performed in families with clustering of late-onset endometrial carcinoma.
Penicillin is necessary for suspected meningococal disease
Authors: V. Hollyoak, A. Gunn
Journal: BMJ (1995)

Amoxycillin 34 (29 6) 2274 (86.2) 1190 (83 6) 1084 (89 3) 172 (915) Co-amoxiclav 6 (5 2) 434 (16 5) 232 (16 3) 202 (16 6) 94 (50 0) Co-trimoxazole 79 (68 7) 1329 (50 4) 726 (51 0) 603 (49 7) 71 (37 8) Erythromycin 112 (97 4) 2284 (86-6) 1231 (86 4) 1053 (86 7) 151 (80 3) Tetracycline 34 (29 6) 343 (13-0) 159 (11-2) 184 (15-2) 25 (13-3) Trimethoprim 24 (20 9) 1024 (38 8) 521 (36 6) 503 (41-4) 85 (45 2) Cephalosporins 63 (54 8) Data not aggregated in these surveys 35 (18-6) Metronidazole 18 (15-7) 409 (15-5) 228 (16-0) 181 (14-9) 1 (0 5) Chloramphenicol: Oral 12 (10-4) Topical 3(2 6)
A rapid and sensitive determination of paclitaxel in rat plasma by UPLC-MS/MS method: Application to a pharmacokinetic study
Authors: He Lian, Jin Sun, Tianhong Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2013)

A rapid and sensitive method for quantitative determination of paclitaxel in rat plasma was developed and validated by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Docetaxel was used as an internal standard and diethyl ether was the liquid–liquid extraction agent. Multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI) was applied to detect paclitaxel and IS at the transitions m/z 854 → 286 and m/z 808.48 → 527.3, respectively. This method covered a linearity range from 5 to 5000 ng/ml, with the total run time of 3.0 min. In summary, a high-throughout UPLC-MS/MS method was successfully developed to measure paclitaxel in rat plasma and was applied to pharmacokinetic study after intravenous administration of paclitaxel.
Influence of orocaecal transit time on hydrogen excretion after carbohydrate malabsorption.
Authors: J J Rumessen, O Hamberg, E Gudmand-Hoyer
Journal: Gut (1989)

The aim of the present study was to determine whether changes in orocaecal transit time (OCTT) affect the magnitude of the breath hydrogen (H2) excretion after ingestion of unabsorbable carbohydrate. We studied eight healthy subjects by interval sampling of end expiratory H2 concentration for 12 hours after ingestion of: (1) 10 g lactulose (L); (2) 10 g L with 20 mg metoclopramide (M) as tablets; (3) 20 g L, and (4) 20 g L with 7.5 mg diphenoxylate (D) as tablets, in random order. In spite of significant changes in OCTT after M and D, there were no significant changes, compared for the same dose of lactulose, with respect to area under the breath H2 excretion curves, peak increments of H2 concentration or timing of the peak increment. We conclude that, within the ranges observed, the OCTT does not significantly affect the shape of the H2 concentration versus time curves. In comparative studies estimates of the degree of carbohydrate malabsorption on the basis of breath H2 concentration may be valid in spite of differences in OCTT.
Colchicine Reduces Postoperative Atrial Fibrillation
Authors: Massimo Imazio, Antonio Brucato, Paolo Ferrazzi, Maria Elena Rovere, Anna Gandino, Roberto Cemin, Stefania Ferrua, Riccardo Belli, Silvia Maestroni, Caterina Simon, Edoardo Zingarelli, Alberto Barosi, Fabrizio Sansone, Davide Patrini, Ettore Vitali, Rita Trinchero, David H. Spodick, Yehuda Adler
Journal: Circulation (2011)

Inflammation and pericarditis may be contributing factors for postoperative atrial fibrillation (POAF), and both are potentially affected by antiinflammatory drugs and colchicine, which has been shown to be safe and efficacious for the prevention of pericarditis and the postpericardiotomy syndrome (PPS). The aim of the Colchicine for the Prevention of the Post-Pericardiotomy Syndrome (COPPS) POAF substudy was to test the efficacy and safety of colchicine for the prevention of POAF after cardiac surgery.The COPPS POAF substudy included 336 patients (mean age, 65.7±12.3 years; 69% male) of the COPPS trial, a multicenter, double-blind, randomized trial. Substudy patients were in sinus rhythm before starting the intervention (placebo/colchicine 1.0 mg twice daily starting on postoperative day 3 followed by a maintenance dose of 0.5 mg twice daily for 1 month in patients ≥70 kg, halved doses for patients <70 kg or intolerant to the highest dose). The substudy primary end point was the incidence of POAF on intervention at 1 month. Despite well-balanced baseline characteristics, patients on colchicine had a reduced incidence of POAF (12.0% versus 22.0%, respectively; P=0.021; relative risk reduction, 45%; number needed to treat, 11) with a shorter in-hospital stay (9.4±3.7 versus 10.3±4.3 days; P=0.040) and rehabilitation stay (12.1±6.1 versus 13.9±6.5 days; P=0.009). Side effects were similar in the study groups.Colchicine seems safe and efficacious in the reduction of POAF with the potentiality of halving the complication and reducing the hospital stay.
Half-cocked T reg cells
Authors: Heather L. Van Epps
Journal: The Journal of Experimental Medicine (2006)

Sarcoidosis is a mysterious, long-recognized disease characterized by the formation of tuberculosis-like granulomas in the lungs. The mystery of sarcoidosis stems from both its unknown etiology and its paradoxical effects on the immune system. The disease has been attributed to a hyperactivation of CD4+ T helper type 1 cells that infiltrate the lungs but, in patients with sarcoidosis, these very cells fail to proliferate in response to recall antigens.






Figure 1

Regulatory T cells (red), shown in a sarcoidosis granuloma, inhibit T cell proliferation, but not their cytokine production.




On page 359, Miyara and colleagues suggest that half-cocked regulatory T (T reg) cells that inhibit proliferation by T cells but not their cytokine production might be to blame for this immune contradiction.

T reg cells normally help suppress chronic inflammation by inhibiting both effector T cell proliferation and cytokine production. Miyara et al. now show that although T reg cell numbers are elevated in both the blood and the lungs of patients with sarcoidosis, these cells were unable to curb the CD4+ T cell production of TNF and interferon (IFN)-γ—inflammatory cytokines that drive the formation and maintenance of granulomas. However, the patients' T reg cells could still shut down effector T cell proliferation, possibly explaining the inability of T cells to respond to recall antigens.

The mechanism behind the T reg cell defect in patients with sarcoidosis remains to be defined, but might be a byproduct of chronic inflammation, as half-active T reg cells have also been found in autoimmune inflammatory diseases such as rheumatoid arthritis and multiple sclerosis.
Painful diabetic neuropathy
Authors: A. Peltier, S. A. Goutman, B. C. Callaghan
Journal: BMJ (2014)

Diabetes is a worldwide epidemic, and associated neuropathy is its most costly and disabling complication. Given the rising prevalence of painful diabetic neuropathy, it is increasingly important that we understand the best ways to diagnose and treat this condition. Diagnostic tests in this field are evolving rapidly. These include the use of skin biopsies to measure small unmyelinated fibers, as well as even newer techniques that can measure both small unmyelinated fibers and large myelinated fibers in the same biopsy. The main treatments for painful diabetic neuropathy remain management of the underlying diabetes and drugs for the relief of pain. However, emerging evidence points to major differences between type 1 and type 2 diabetes, including the ability of glycemic control to prevent neuropathy. Enhanced glucose control is much more effective at preventing neuropathy in patients with type 1 diabetes than in those with type 2 disease. This dichotomy emphasizes the need to study the pathophysiologic differences between the two types of diabetes, because different treatments may be needed for each condition. The impact of the metabolic syndrome on neuropathy in patients with type 2 diabetes may account for the difference between the two types of diabetes and requires further study. Finally, neuropathic pain is under-recognized and undertreated despite an ever evolving list of effective drugs. Evidence exists to support several drugs, but the optimal sequence and combination of these drugs are still to be determined.
High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis
Authors: Richard A. Nash, James D. Bowen, Peter A. McSweeney, Steven Z. Pavletic, Kenneth R. Maravilla, Man-soo Park, Jan Storek, Keith M. Sullivan, Jinan Al-Omaishi, John R. Corboy, John DiPersio, George E. Georges, Theodore A. Gooley, Leona A. Holmberg, C. Fred LeMaistre, Kate Ryan, Harry Openshaw, Julie Sunderhaus, Rainer Storb, Joseph Zunt, George H. Kraft
Journal: Blood (2003)