tbuckley/cabot-search huggingface dataset:
Lysophospholipid signaling in the function and pathology of the reproductive system
Authors: X. Ye
Journal: Human Reproduction Update (2008)

Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are two prominent signaling lysophospholipids (LPs) exerting their functions through a group of G protein-coupled receptors (GPCRs). This review covers current knowledge of the LP signaling in the function and pathology of the reproductive system.PubMed was searched up to May 2008 for papers on lysophospholipids/LPA/S1P/LPC/SPC in combination with each part of the reproductive system, such as testis/ovary/uterus.LPA and SIP are found in significant amounts in serum and other biological fluids. To date, 10 LP receptors have been identified, including LPA(1-5) and S1P(1-5). In vitro and in vivo studies from the past three decades have demonstrated or suggested the physiological functions of LP signaling in reproduction, such as spermatogenesis, male sexual function, ovarian function, fertilization, early embryo development, embryo spacing, implantation, decidualization, pregnancy maintenance and parturition, as well as pathological roles in ovary, cervix, mammary gland and prostate cancers.Receptor knock-out and other studies indicate tissue-specific and receptor-specific functions of LP signaling in reproduction. More comprehensive studies are required to define mechanisms of LP signaling and explore the potential use as a therapeutic target.
Functional expression of an inactivating potassium channel cloned from human heart.
Authors: S Po, D J Snyders, R Baker, M M Tamkun, P B Bennett
Journal: Circulation Research (1992)

Recently a putative K+ channel with homology to the Shaker family of potassium channels has been cloned from human ventricular myocardium. However, proof that the cDNA encodes a K+ channel requires appropriate translation and expression of a functional ion-selective channel. Therefore, expression of this putative human K+ channel DNA was attempted by cytoplasmic injections of in vitro transcribed cRNA into Xenopus laevis oocytes and screening by two-electrode voltage-clamp methods. This resulted in expression of voltage-gated channels that rapidly inactivated (time constant of inactivation, 47.6 +/- 3.6 msec; 0 mV; n = 10) and were at least 50 times more selective for K+ than Na+ (Na+/K+ permeability ratio of 0.02). The channels showed voltage-dependent activation (half-maximal voltage, -34 +/- 0.7 mV; n = 5), and 50% of the channels were inactivated within 2 seconds when the membrane potential was clamped near -60 mV (half-maximal voltage, -62 +/- 7 mV; n = 10). The expressed protein resulted in a K+ current that had many properties similar to the 4-aminopyridine-sensitive calcium-insensitive component of the cardiac transient outward current that is observed in native cardiac myocytes and thus may serve as one molecular substrate for this current.
CASE OF EXTERNAL URETHROTOMY TREATED BY CONTINUOUS RETENTION OF A RUBBER CATHETER HELD IN POSITION BY A "PERINEAL STOP."
Authors: C. H. Whiteford
Journal: BMJ (1903)

Lm 1399 pain and irritability of the bladder, and in August, 1899, he was laid aside by a severe and persistent attack lasting thirteen days.I first saw him on October zoth, 1899.He usually saw blood every day or so, sometimes every time he made water, and was unable on this account, as well as from the pain, frequency of micturition, and straining, to satisfactcrily carry on his usual occupation.I examined his bladder and removed many ffe specimens of papilloma.The urine contained pus.He questioned me as to the advisability under the circumstances of another operation, and I suggested as an alternative that he should try the effect of nitrate of silver injections.I therefore taught him the method, commencing with i gr. to 4 oz. of warm water, and increased the strength daily.He returned home in the course of a week carrying out the treatment.January 25th, I900.He reports "'the best month since December (896."He has, injected regularly, UsiDg Ii4 gr. of the silver nitrate.The blood has steadily decreased in frequency and amount, a period of a week often elapsing without any symptom, and then only a drop or two of pure blood coming at the end of micturition.The other bladder troubles had also become much less pronounced.During the early part of the treatment he had voided many fragments of tumour, exhibiting the usual changes.September 2gth.Two gr. of silver nitrate have been injected daily.No blood has been seen for a month and the other symptoms have quite subsided.The urine is not quite clear for it contains pus.May 24th, I9OI.The patient writes "I am surprisingly well."He has made no injection since the last report.
The Risk of Cancer in Users of Statins
Authors: Matthijs R. Graaf, Annette B. Beiderbeck, Antoine C.G. Egberts, Dick J. Richel, Henk-Jan Guchelaar
Journal: Journal of Clinical Oncology (2004)

Purpose Several preclinical studies suggested a role for 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the treatment of cancer. The objective of this study was to compare the risk of incident cancer between users of statins and users of other cardiovascular medication. Methods Data were used from the PHARMO database, containing drug dispensing records from community pharmacies and linked hospital discharge records for residents of eight Dutch cities. The study base included all patients with one or more prescriptions for cardiovascular drugs in the period between January 1, 1985 and December 31, 1998. Cases were identified as patients in the study base with a diagnosis of incident cancer and matched with four to six controls on sex, year of birth, geographic region, duration of follow-up, and index date. The analysis was adjusted for diabetes mellitus; prior hospitalizations; comorbidity; and use of diuretics, angiotensin-converting enzyme inhibitors, calcium-channel blockers, nonsteroidal anti-inflammatory drugs, sex hormones, and other lipid-lowering drug therapies. Results In the study base, 3,129 patients were identified and matched to 16,976 controls. Statin use was associated with a risk reduction of cancer of 20% (adjusted odds ratio [OR], 0.80; 95% CI, 0.66 to 0.96). Our data suggest that statins are protective when used longer than 4 years (adjusted OR, 0.64; 95% CI, 0.44 to 0.93) or when more than 1,350 defined daily doses are taken (adjusted OR, 0.60; 95% CI, 0.40 to 0.91). Conclusion This observational study suggests that statins may have a protective effect against cancer.
Risk of thromboembolic events after recurrent spontaneous abortion in antiphospholipid syndrome: a case–control study
Authors: Maria Angeles Martinez-Zamora, Sara Peralta, Montserrat Creus, Dolors Tassies, Juan Carlos Reverter, Gerard Espinosa, Ricard Cervera, Francisco Carmona, Juan Balasch
Journal: Annals of the Rheumatic Diseases (2011)

To investigate whether patients having antiphospholipid syndrome (APS) as the only aetiological factor for recurrent spontaneous abortion (RSA) are at increased risk of thrombosis later in life.A case-control study at a tertiary university referral centre. The study group consisted of 57 primary APS and RSA women (APS-RSA group). Control groups included: 86 patients with RSA of unknown aetiology (uRSA group), 42 patients with RSA and thrombophilic genetic defects as the only aetiologic factor for RSA (tRSA group) and 30 antiphospholipid antibody (aPL) positive but otherwise healthy women (aPL group). The main measurement was the thrombosis rate after long-term follow-up.APS-RSA patients had a significantly higher 12-year cumulative thrombotic incidence rate compared with the three comparator groups (19.3% vs 4.8%, 0.0% and 0.0%, respectively (log rank), p<0.001). Patients in the APS-RSA group had 25.6 thrombotic events per 1000 patient-years (95% CI 12.8 to 45.9). The OR of thrombosis in relation to the presence (APS-RSA group) or absence (uRSA and tRSA groups) of aPL in patients with RSA was 15.06 (95% CI 3.2 to 70.5).Our data indicate that a history of RSA associated with aPL is a risk factor for subsequent thrombosis in the long term.
Diastolic perfusion time at ischemic threshold in patients with stress-induced ischemia.
Authors: G Ferro, L Spinelli, C Duilio, M Spadafora, F Guarnaccia, M Condorelli
Journal: Circulation (1991)

To evaluate the relevance of diastolic perfusion time on the mechanisms underlying stress-induced ischemia, 16 patients with coronary artery disease and seven patients with syndrome X underwent five randomized stress tests (upright and supine exercise with and without therapy, transesophageal atrial pacing).Exercise duration Time to 0.1 mV ST segment depression, heart rate, rate-pressure product, and diastolic perfusion time were evaluated for each patient during stress tests. In both groups, variability coefficients of the above-mentioned parameters were not different at rest. At ischemic threshold (0.1 mV ST segment depression) in patients with coronary artery disease, the variability coefficient of exercise duration (40.1 +/- 22.2) was significantly higher (p less than 0.0001) than those of heart rate (12.8 +/- 2.9), rate-pressure product (14.8 +/- 3.3), and diastolic perfusion time (0.39 +/- 0.1). The variability coefficient of diastolic perfusion time was also significantly (p less than 0.0001) lower than those of heart rate and rate-pressure product. Similarly, the variability coefficient of diastolic perfusion time (0.44 +/- 0.1) in syndrome X patients was significantly lower (p less than 0.0001) than those of exercise duration (28.2 +/- 9.4), heart rate (12 +/- 1.4), and rate-pressure product (14.6 +/- 1.3).Fixed diastolic perfusion time at ischemic threshold, despite different kinds of stress tests and variability of heart rate and rate-pressure product, indicates the relevant role of diastolic perfusion time in determining myocardial ischemia.
Building a data sharing model for global genomic research
Authors: Patricia Kosseim, Edward S Dove, Carman Baggaley, Eric M Meslin, Fred H Cate, Jane Kaye, Jennifer R Harris, Bartha M Knoppers
Journal: Genome biology (2014)

Data sharing models designed to facilitate global business provide insights for improving transborder genomic data sharing. We argue that a flexible, externally endorsed, multilateral arrangement, combined with an objective third-party assurance mechanism, can effectively balance privacy with the need to share genomic data globally.
Motor and cognitive deficits in aged tau knockout mice in two background strains
Authors: Peng Lei, Scott Ayton, Steve Moon, Qihao Zhang, Irene Volitakis, David I Finkelstein, Ashley I Bush
Journal: Molecular Neurodegeneration (2014)

We recently reported that Parkinsonian and dementia phenotypes emerge between 7-12 months of age in tau-/- mice on a Bl6/129sv mixed background. These observations were partially replicated by another group using pure Bl6 background tau-/- mice, but notably they did not observe a cognitive phenotype. A third group using Bl6 background tau-/- mice found cognitive impairment at 20-months of age. To reconcile the observations, here we considered the genetic, dietary and environmental variables in both studies, and performed an extended set of behavioral studies on 12-month old tau+/+, tau+/-, and tau-/- mice comparing Bl6/129sv to Bl6 backgrounds. We found that tau-/- in both backgrounds exhibited reduced tyrosine hydroxylase-positive nigral neuron and impaired motor function in all assays used, which was ameliorated by oral treatment with L-DOPA, and not confounded by changes in body weight. Tau-/- in the C57BL6/SV129 background exhibited deficits in the Y-maze cognition task, but the mice on the Bl6 background did not. These results validate our previous report on the neurodegenerative phenotypes of aged tau-/- mice, and show that genetic background may impact the extent of cognitive impairment in these mice. Therefore excessive lowering of tau should be avoided in therapeutic strategies for AD.
Effects of Multiple Pituitary Homografts or Progesterone on 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene-lnduced Mammary Tumors in Rats&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Clifford W. Welsch, James A. Clemens, Joseph Meites
Journal: JNCI Journal of the National Cancer Institute (1968)

This investigation evaluates the effects of prolactin-secreting pituitary homografts and progesterone on the induction of mammary tumors in female rats subsequently treated with 7,12-dimethylbenz[a]anthracene (DMBA). Immature female Sprague-Dawley rats were divided into 5 groups: group I, intact controls; group II, ovariectomized; group III, intact and 4 pituitary homografts, group IV, ovariectomized and 4 pituitary homografts; and group V, intact and given injection of 4 mg progesterone daily. Pituitary transplantation and/or ovariectomy were performed at age 25 days. Progesterone was injected beginning at 30 days of age and continued for 40 consecutive days. At age 55 days, all animals were given a single iv dose of 5 mg DMBA. At the end of the study, percent tumor incidence, average number of tumors per rat, and average total weight of tumors per rat (g) were: group I,100%, 12.2 ± 1.2, 16.2 ± 3.5; group II, 0; group III, 73%, 4.7 ± 1.3, 5.4 ± 2.0; group IV, 0; and group V, 79%, 3.3 ± 0.7, 5.9 ± 4.6. Percentage of rats with tumors, average number of tumors per rat, and average total weight of tumors per rat were significantly decreased in intact rats bearing 4 pituitary homografts, and in intact rats given injections of progesterone, as compared to the intact controls. The inhibitory effect of the prolactin-secreting pituitary homografts appears to be mediated at least in part through the ovary, since daily injections of progesterone resulted in a comparable inhibition of mammary tumorigenesis. These data indicate that prolactin and/or progesterone, by stimulating growth and development of the mammary gland, inhibit DMBA-induced mammary tumorigenesis if given sufficiently before carcinogen treatment.
Medulloblastoma Variants: Age-Dependent Occurrence and Relation to Gorlin Syndrome—A New Clinical Perspective
Authors: Maria Luisa Garrè, Armando Cama, Francesca Bagnasco, Giovanni Morana, Felice Giangaspero, Massimo Brisigotti, Claudio Gambini, Marco Forni, Andrea Rossi, Riccardo Haupt, Paolo Nozza, Salvina Barra, Gianluca Piatelli, GianMaria Viglizzo, Valeria Capra, William Bruno, Lorenza Pastorino, Maura Massimino, Miriam Tumolo, Paola Fidani, Sandro Dallorso, Riccardo Fabian Schumacher, Claudia Milanaccio, Torsten Pietsch
Journal: Clinical Cancer Research (2009)

We aimed to test the hypothesis that medulloblastoma (MB) variants show a different age distribution and clinical behavior reflecting their specific biology, and that MB occurring at very young age is associated with cancer predisposition syndromes such as Gorlin syndrome (GS).We investigated the frequency, age distribution, location, response to treatment, outcome, and association with familial cancer predisposition syndromes in a series of 82 cases of MB in patients ages <14 years diagnosed at the Giannina Gaslini Children's Hospital, Genoa, between 1987 and 2004.Desmoplastic MB and MB with extensive nodularity (MBEN), were present in 22 of 82 cases (27%) and were more frequent in children ages <or=3 years (13 of 25; 52%). In this age group, MBEN was significantly more frequent than desmoplastic MB and classic MB (P < 0.001) and had a good prognosis. MBEN was associated with GS in 5 of 12 cases. Overall, 8 cases occurred in the context of familial tumor predisposition syndromes (5 GS, 1 each NF1, Li-Fraumeni, and Fragile X) and 7 of these patients were ages <or=3 years at diagnosis. Desmoplastic histology and a more intensive treatment represented independent favorable prognostic factors in multivariate analysis (P = 0.003 and P = 0.0139, respectively). Metastasis was a predictor of bad outcome (P = 0.0001).Our data indicate that biologically different MB entities warrant risk-adapted treatment and that MBEN is strongly associated with GS. Patients, ages <or=3 years, with MB and their families should be investigated for tumor predisposition syndromes such as GS.
SCN10A/Nav1.8 modulation of peak and late sodium currents in patients with early onset atrial fibrillation
Authors: Eleonora Savio-Galimberti, Peter Weeke, Raafia Muhammad, Marcia Blair, Sami Ansari, Laura Short, Thomas C. Atack, Kaylen Kor, Carlos G. Vanoye, Morten Salling Olesen, None LuCamp, Tao Yang, Alfred L. George, Dan M. Roden, Dawood Darbar
Journal: Cardiovascular Research (2014)

To test the hypothesis that vulnerability to atrial fibrillation (AF) is associated with rare coding sequence variation in the SCN10A gene, which encodes the voltage-gated sodium channel isoform NaV1.8 found primarily in peripheral nerves and to identify potentially disease-related mechanisms in high-priority rare variants using in-vitro electrophysiology. We re-sequenced SCN10A in 274 patients with early onset AF from the Vanderbilt AF Registry to identify rare coding variants. Engineered variants were transiently expressed in ND7/23 cells and whole-cell voltage clamp experiments were conducted to elucidate their functional properties. Resequencing SCN10A identified 18 heterozygous rare coding variants (minor allele frequency ≤1%) in 18 (6.6%) AF probands. Four probands were carriers of two rare variants each and 14 were carriers of one coding variant. Based on evidence of co-segregation, initial assessment of functional importance, and presence in ≥1 AF proband, three variants (417delK, A1886V, and the compound variant Y158D-R814H) were selected for functional studies. The 417delK variant displayed near absent current while A1886V and Y158D-R814H exhibited enhanced peak and late (INa-L) sodium currents; both Y158D and R818H individually contributed to this phenotype. Rare SCN10A variants encoding Nav1.8 were identified in 6.6% of patients with early onset AF. In-vitro electrophysiological studies demonstrated profoundly altered function in 3/3 high-priority variants. Collectively, these data strongly support the hypothesis that rare SCN10A variants may contribute to AF susceptibility.
Essential role of RSK2 in c-Fos–dependent osteosarcoma development
Authors: Jean-Pierre David, Denis Mehic, Latifa Bakiri, Arndt F. Schilling, Vice Mandic, Matthias Priemel, Maria Helena Idarraga, Markus O. Reschke, Oskar Hoffmann, Michael Amling, Erwin F. Wagner
Journal: Journal of Clinical Investigation (2005)

Inactivation of the growth factor–regulated S6 kinase RSK2 causes Coffin-Lowry syndrome in humans, an X-linked mental retardation condition associated with progressive skeletal abnormalities. Here we show that mice lacking RSK2 develop a progressive skeletal disease, osteopenia due to impaired osteoblast function and normal osteoclast differentiation. The phenotype is associated with decreased expression of Phex, an endopeptidase regulating bone mineralization. This defect is probably not mediated by RSK2-dependent phosphorylation of c-Fos on serine 362 in the C-terminus. However, in the absence of RSK2, c-Fos–dependent osteosarcoma formation is impaired. The lack of c-Fos phosphorylation leads to reduced c-Fos protein levels, which are thought to be responsible for decreased proliferation and increased apoptosis of transformed osteoblasts. Therefore, RSK2-dependent stabilization of c-Fos is essential for osteosarcoma formation in mice and may also be important for human osteosarcomas.
Maternal Fish Consumption, Hair Mercury, and Infant Cognition in a U.S. Cohort
Authors: Emily Oken, Robert O. Wright, Ken P. Kleinman, David Bellinger, Chitra J. Amarasiriwardena, Howard Hu, Janet W. Rich-Edwards, Matthew W. Gillman
Journal: Environmental Health Perspectives (2005)

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother–infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples &gt; 1.2 ppm. Mean VRM score was 59.8 (range, 10.9–92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, –13.7 to –1.2) points. VRM scores were highest among infants of women who consumed &gt; 2 weekly fish servings but had mercury levels ≤1.2 ppm. Higher fish consumption in pregnancy was associated with better infant cognition, but higher mercury levels were associated with lower cognition. Women should continue to eat fish during pregnancy but choose varieties with lower mercury contamination.
Identification of a Possible Somatic BRCA1 Mutation Affecting Translation Efficiency in an Early-Onset Sporadic Breast Cancer Patient
Authors: S. Papa, D. Seripa, G. Merla, C. Gravina, V. M. Fazio, M. Giai, P. Sismondi, A. Serra, G. Saglio, M. Rinaldi
Journal: JNCI Journal of the National Cancer Institute (1998)
A case of common variable immunodeficiency presenting with furunculosis
Authors: R.U. Sidwell, M.A.A. Ibrahim, C.B. Bunker
Journal: British Journal of Dermatology (2002)

Journal Article A case of common variable immunodeficiency presenting with furunculosis Get access R.U. Sidwell, R.U. Sidwell Department of Dermatology, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, U.K R.U.Sidwell. Search for other works by this author on: Oxford Academic Google Scholar M.A.A. Ibrahim, M.A.A. Ibrahim Department of Clinical Immunology, King's College Hospital, Denmark Hill, London, SE5 9RS, U.K Search for other works by this author on: Oxford Academic Google Scholar C.B. Bunker C.B. Bunker Department of Dermatology, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 147, Issue 2, 1 August 2002, Pages 364–367, https://doi.org/10.1046/j.1365-2133.2002.04772.x Published: 01 August 2002 Article history Accepted: 03 December 2001 Published: 01 August 2002
Intensive Care of Patients with HIV Infection
Authors: Laurence Huang, Andrew Quartin, Denis Jones, Diane V. Havlir
Journal: New England Journal of Medicine (2006)

The intensive care of patients with human immunodeficiency virus (HIV) infection is increasingly complex and may involve difficult decisions about the initiation or continuation of antiretroviral therapy. In some critically ill patients, the diagnosis of HIV has not been established, and there are legal implications for many important clinical decisions. Care may also be complicated by HIV-related pulmonary, cardiac, or renal impairment.
Evaluation of a panel of non-invasive serum markers to differentiate mild from moderate-to-advanced liver fibrosis in chronic hepatitis C patients
Authors: Keyur Patel, Stuart C. Gordon, Ira Jacobson, Christophe Hézode, Esther Oh, Katie M. Smith, Jean-Michel Pawlotsky, John G. McHutchison
Journal: Journal of Hepatology (2004)