tbuckley/cabot-search huggingface dataset:
O-GlcNAcylation contributes to the vascular effects of ET-1 via activation of the RhoA/Rho-kinase pathway
Authors: Victor V. Lima, Fernanda R. Giachini, Fernando S. Carneiro, Maria Helena C. Carvalho, Zuleica B. Fortes, R. Clinton Webb, Rita C. Tostes
Journal: Cardiovascular Research (2010)

Glycosylation with β-N-acetylglucosamine (O-GlcNAcylation) is one of the most complex post-translational modifications. The cycling of O-GlcNAc is controlled by two enzymes: UDP-NAc transferase (OGT) and O-GlcNAcase (OGA). We recently reported that endothelin-1 (ET-1) augments vascular levels of O-GlcNAcylated proteins. Here we tested the hypothesis that O-GlcNAcylation contributes to the vascular effects of ET-1 via activation of the RhoA/Rho-kinase pathway.Incubation of vascular smooth muscle cells (VSMCs) with ET-1 (0.1 μM) produces a time-dependent increase in O-GlcNAc levels. ET-1-induced O-GlcNAcylation is not observed when VSMCs are previously transfected with OGT siRNA, treated with ST045849 (OGT inhibitor) or atrasentan (ET(A) antagonist). ET-1 as well as PugNAc (OGA inhibitor) augmented contractions to phenylephrine in endothelium-denuded rat aortas, an effect that was abolished by the Rho kinase inhibitor Y-27632. Incubation of VSMCs with ET-1 increased expression of the phosphorylated forms of myosin phosphatase target subunit 1 (MYPT-1), protein kinase C-potentiated protein phosphatase 1 inhibitor protein (protein kinase C-potentiated phosphatase inhibitor-17), and myosin light chain (MLC) and RhoA expression and activity, and this effect was abolished by both OGT siRNA transfection or OGT inhibition and atrasentan. ET-1 also augmented expression of PDZ-Rho GEF (guanine nucleotide exchange factor) and p115-Rho GEF in VSMCs and this was prevented by OGT siRNA, ST045849, and atrasentan.We suggest that ET-1 augments O-GlcNAcylation and this modification contributes to increased vascular contractile responses via activation of the RhoA/Rho-kinase pathway.
Isolation and culture of follicular papillae from murine vibrissae: an introductory approach
Authors: D. WILLIAMS, K. PROFETA, K.S. STENN
Journal: British Journal of Dermatology (1994)

The recent successes in culturing follicular papilla cells have afforded a rapid advance in our understanding of hair biology. Although the experimental manipulation of the papilla is briefly described in the original reports, a detailed description for workers starting in the field is not yet available. In this report we give a brief review of hair biology relevant to the papilla, and illustrate the method we have found successful for isolating and growing papilla cells.
Taking the sting out of lumbar puncture
Authors: P. Rizzoli
Journal: BMJ (2013)

Ultrasound guided procedures seem less likely to fail 

Lumbar puncture remains an important and commonly performed diagnostic procedure,1 but training for its performance is not standardized.2 Although most diagnostic lumbar punctures are performed by neurologists, hospitalists, emergency department physicians, and pediatricians, physicians in many different specialties should have some experience with lumbar punctures and may on occasion need to perform one.

A well designed linked systematic review and meta-analysis by Shaikh and colleagues (doi:10.1136/bmj.f1720) investigates the benefit of using ultrasound guidance when performing lumbar puncture in routine diagnostic and therapeutic settings and in the performance of epidural catheterizations, mainly for giving anesthesia.3 The meta-analysis looked at 14 randomized studies with results from more than 1300 participants. It found a significant risk reduction for the primary outcome measure of failed procedures for ultrasound guided compared with the traditional anatomic approach to lumbar puncture. Failed procedures were defined conservatively as any failure to achieve the goals intended for the procedure. Epidural catheterizations were judged equivalent …
Founding Date of the Pennsylvania Hospital
Authors: W. F. Norwood
Journal: JAMA (1964)

It is true that a charter from the General Assembly was approved by the governor of the colony on May 11, 1751. According to Benjamin Franklin's early historical sketch of the Pennsylvania Hospital, substantial agitation for a hospital began in late 1750 and a petition was presented to the Assembly in early 1751. During the summer and fall months, the Board of Managers busied themselves with raising money, looking for a site, etc. In October it was agreed to rent temporary quarters, select a staff, and begin the alterations of a large residence to be used until sufficient funds would be available for construction of a building. On Jan 13, 1752, the "Contributors" (the corporate body) met and agreed on the limitations of the power and duty of the "Managers" and other personnel. On Feb 6 the Chief Justice approved of the proposed rules for admission of patients and on
Ten year cerebrovascular morbidity and mortality in 68 year old men with asymptomatic carotid stenosis
Authors: M. Ogren, B. Hedblad, S.-O. Isacsson, L. Janzon, G. Jungquist, S.-E. Lindell
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To study the natural course of carotid artery stenosis detected by ultrasonography. <b>Design</b>: Prospective cohort study. Baseline examination in 1982-3 included ultrasound examination of carotid arteries, measurement of anklebrachial blood pressure index, and detection of atrial fibrillation by 24 hour ambulatory electrocardiography. <b>Setting</b>: Malmo, a city in southern Sweden with 230000 inhabitants. <b>Subjects</b>: 470 men aged 68 years randomly selected from the population. <b>Main outcome measures</b>: Incidence of stroke and transient ischaemic attack and all cause mortality during 10 years of follow up in relation to carotid stenosis, leg artery disease (ankle-brachial blood pressure index below 0.9), and atrial fibrillation. <b>Results</b>: Fifty men had a stroke; six of these were haemorrhagic. Another 11 had a transient ischaemic attack. Eighteen of the men with carotid stenosis (21.6 events/1000 person years) and 43 of the men with normal carotid arteries (14.8 events/1000 person years) had a stroke or transient ischaemic attack (P=0.188). Men with atrial fibrillation had an increased rate of cerebrovascular events (36.7/1000 person years (P=0.048). The highest rate was found in men with asymptomatic disease of the leg arteries (38.6/1000 person years) (P&lt;0.001). The increased risk of stroke or transient ischaemic attack in this group remained after multivariate analysis (relative risk 2.0; 95% confidence interval 1.1 to 3.7). <b>Conclusions</b>: In this cohort carotid stenosis was not associated with an increased risk of stroke. Part of this lack of association was explained by the high mortality from ischaemic heart disease in men with severe stenosis. Twenty seven of the 61 cerebrovascular events, however, occurred in men who had normal carotid arteries, normal ankle pressure, and no atrial fibrillation. <h3>Key messages</h3> Key messages Asymptomatic atherosclerosis in carotid and leg arteries is a common occurrence among elderly people Both conditions were found to be associated with an excess cardiovascular mortality Compared with leg artery disease, asymptomatic carotid stenosis was not found to be associated with an increased risk of stroke Assessment of peripheral atherosclerotic disease by measurement of arm and ankle blood pressure is a useful method for identifying patients with an increased risk of stroke
Selfish goals must compete for the common currency of reward
Authors: George Ainslie
Journal: Behavioral and Brain Sciences (2014)

Abstract Selfish Goal Theory is compatible with a behaviorally based theory that recognizes mental processes as behaviors. Both envision choices as made by the competition of purposive processes, which are autonomous in that they are not coordinated by an agentic “self.” However, the survival of mental processes – termed “goals” or “interests,” respectively – depends on a well-documented active mechanism: reward.
Vertebral rim lesions in dorsolumbar spine.
Authors: B Vernon-Roberts
Journal: Annals of the Rheumatic Diseases (1984)

Royal National Hospital for Rheumatic Diseases we found 2 Schmorl G. Junghanns H. Ile Iiieit ma spine in lien/iltl, 01(1 differences between the seropositive and seronegative disease.2nd American edition translaited aind editcd by E F patients that to some extent paralleled our original
Modulation of the hyperpolarization-activated current (If) by calcium and calmodulin in the guinea-pig sino-atrial node
Authors: L Rigg
Journal: Cardiovascular Research (2003)

The aim of this study was to investigate possible regulation of the hyperpolarization-activated current (If) by cytosolic calcium in guinea-pig sino-atrial (SA) node cells. Isolated SA node cells were superfused with physiological saline solution (36 °C) and the perforated patch voltage-clamp technique used to record If activated by hyperpolarizing voltage steps. A 10-min loading of SA node cells with the calcium chelator BAPTA (using 10 μM BAPTA-AM) significantly reduced the amplitude of If at all potentials studied (69±8% at −80 mV, n=6). BAPTA loading also shifted the voltage of half-activation (Vh) of the conductance from −83±2 mV in control to −93±2 mV in BAPTA (n=6) without significantly altering the slope of activation. The calmodulin antagonists W-7 (10 μM), calmidazolium (25 μM) and ophiobolin A (20 μM) caused similar reductions in If amplitude (73±4, 86±9 and 59±6% at −80 mV, n=6, 5 and 4, respectively) and shifts in Vh (11±3, 14±3 and 8±2 mV). In cells pre-treated with W-7, exposure to BAPTA caused no further reduction in current amplitude (n=6). If current amplitude was unaffected by the calmodulin dependent kinase (CaMKII) inhibitor KN-93 (1 μM) although this CaMKII inhibition did reduce L-type calcium by 48±19% at 0 mV (n=3). These results are consistent with a role for calcium and calmodulin in the regulation of If, via a mechanism that is independent of CaMKII. Alterations in intracellular calcium during the cardiac cycle may be involved in fine tuning the voltage-dependent properties of If and may thus determine its relative contribution to pacemaking in the SA node.
Britain tops Europe for childhood skin cancer
Authors: Roger Dobson
Journal: BMJ (2006)

The British Isles has the highest rates of skin cancer in children and adolescents in Europe, a study has found ( European Journal of Cancer 2006;42:2170-82).

The incidence of malignant melanoma in adolescents is also increasing faster in the British Isles than in other regions, the study concludes, based on cases in 20 European countries.

On average, the incidence in Europe increased annually in adolescents, by 4.1% for melanoma and 2.5% for skin carcinoma, between 1978 and 1997.

“Increases in incidence over time were observed only for adolescents, possibly reflecting a change in risk factors relevant to adolescents and adults, but not to children,” say the authors, from the Erasmus Medical Centre and the Comprehensive Cancer Centre South in the Netherlands; the International Agency for Research on Cancer and the Gustave-Roussy Institute in …
SURGICAL CONSIDERATIONS OF CARCINOMATOUS METASTASES TO THE BRAIN
Authors: ERIC OLDBERG
Journal: JAMA (1933)

In 1926, Francis Grant,<sup>1</sup>in a review of the forty-nine cases of intracranial malignant metastases which had been seen in the service of Dr. Harvey Cushing up to that year, concluded that "Surgery, whether radical or palliative, is of no ultimate benefit to these patients so far as prolongation of life is concerned." He felt justified in making this conclusion because his statistics showed that the average period of survival from hospitalization to death of persons afflicted with such lesions was three months, irrespective of whether the metastases were treated, decompressed or left alone. A further study from the same clinic in 1931 by Meagher and Eisenhardt<sup>2</sup>lent weight to his figures by showing that of the ten cases in which the primary focus lay in the breast, the longest period of survival following operation was five months, the average being six weeks. Since the publication of these
Relationship Between Regional Per Capita Medicare Expenditures and Patient Perceptions of Quality of Care
Authors: Floyd J. Fowler
Journal: JAMA (2008)

Wide variations in Medicare expenditures exist across regions, but little is known about whether beneficiaries residing in low-expenditure regions perceive receiving lower-quality care than those in high-expenditure regions.To evaluate how Medicare beneficiaries' perceptions of their health care are related to per capita expenditure in the areas where they live. DESIGN, SETTING, AND RESPONDENTS: A probability sample of Medicare beneficiaries living in households in the United States was surveyed by a combination of mail and telephone in 2005. Each respondent was allocated to 1 of 5 quintiles, depending on mean age-, sex-, and race-adjusted per capita Medicare expenditures based on Centers for Medicare & Medicaid Services claims data.The survey included 3 questions about perceived unmet need for care, 4 questions about the perceived quality of ambulatory care, and 3 questions rating the perceived quality of overall care.Of 4000 Medicare beneficiaries sampled, 160 (4%) were ascertained to have died or to be living in a long-term care facility. Of the remaining 3840 potentially eligible beneficiaries, 2515 (65%) responded. Per capita expenditures were highly related to receiving more medical care, such as mean number of ambulatory visits to physicians in the past year (range from lowest to highest expenditure quintile, 3.4-3.9; P < .001 for linear trend) and more cardiac tests (respondents reporting receiving tests in past year, 158/387 [40.1%] to 468/739 [63.5%]; P < .001 for linear trend). However, 7 of the 10 measures of perceived quality, including perceived unmet needs for tests and treatment (respondents reporting unmet needs, 15/387 [3.9%] to 37/739 [5.0%]; P = .25 for linear trend) and spending enough time with physicians (respondents reporting adequate time, 311/387 [88.7%] to 603/739 [87.0%]; P = .94 for linear trend), were unrelated to expenditures, while the overall rating of perceived quality of care was higher in the lower-expenditure areas (respondents reporting overall care rating of 9 or 10, 242/387 [63.3%] to 404/739 [55.4%]; P = .008 for linear trend).In this representative sample of Medicare beneficiaries, no consistent association was observed between the mean per capita expenditure in a geographic area and the perceptions of the quality of medical care of the people who live in those areas.
Proteolytic processing of CXCL11 by CD13/aminopeptidase N impairs CXCR3 and CXCR7 binding and signaling and reduces lymphocyte and endothelial cell migration
Authors: Paul Proost, Anneleen Mortier, Tamara Loos, Jo Vandercappellen, Mieke Gouwy, Isabelle Ronsse, Evemie Schutyser, Willy Put, Marc Parmentier, Sofie Struyf, Jo Van Damme
Journal: Blood (2007)
Reply to Krabshuis
Authors: R. Kiley
Journal: Endoscopy (1998)

See also: Reply to KileyEndoscopy 1998; 30(07): 667-667DOI: 10.1055/s-2007-1001375 See also: Endoscopy Information Online: Can Endoscopists Close the Gap Between What is Known and What They Do?Endoscopy 1997; 29(09): 871-882DOI: 10.1055/s-2007-1004324
Zygotic-Splitting Rates after Single-Embryo Transfers in in Vitro Fertilization
Authors: Isaac Blickstein, Christopher Jones, Louis G. Keith
Journal: New England Journal of Medicine (2003)

To the Editor: The mechanism of spontaneous monozygotic twinning is unknown. However, on the basis of observations first made 15 years ago, it is now generally accepted that all forms of assisted conception increase the rate of zygotic splitting.1–3 The true incidence of zygotic splitting is unknown in a substantial proportion of twins, because same-sex dizygotic twins cannot be differentiated from dichorionic monozygotic twins by either antepartum ultrasonography4 or postpartum clinical examination. Single-embryo transfers are currently considered to be a means for minimizing the risk of multiple births with in vitro fertilization. In order to assess the risk of . . .
Challenges in inhaled product development and opportunities for open innovation
Authors: Ben Forbes, Bahman Asgharian, Lea Ann Dailey, Douglas Ferguson, Per Gerde, Mark Gumbleton, Lena Gustavsson, Colin Hardy, David Hassall, Rhys Jones, Ruth Lock, Janet Maas, Tim McGovern, Gary R. Pitcairn, Graham Somers, Ron K. Wolff
Journal: Advanced Drug Delivery Reviews (2010)
Urinary 5-hydroxyindole acetate concentration in pregnancy induced hypertension.
Authors: G. M. Filshie, P. Maynard, C. Hutter, J. C. Cooper, G. Robinson, P. Rubin
Journal: BMJ (1992)

study of past casualties.For example, our data indicate that a programme ofpreventing heroin use in the 1990s will be ineffective if it focuses on injecting: initiation into heroin use is now by chasing, and the progression (or non-progression) to injecting occurs at a later stage through influences of which we know little.We are grateful to the Department of Health for research grant support.The views expressed are those of the authors.1 Parker H, Newcombe R, Bakx K.The new heroin users: prevalence and
Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy.
Authors: M Mizutani, T S Kern, M Lorenzi
Journal: Journal of Clinical Investigation (1996)

To reconstruct the mechanisms for the vasoobliteration that transforms diabetic retinopathy into an ischemic retinopathy, we compared the occurrence of cell death in situ in retinal microvessels of diabetic and nondiabetic individuals. Trypsin digests and sections prepared from the retinas of seven patients (age 67 +/- 7 yr) with .9 +/- 4 yr of diabetes and eight age- and sex-matched nondiabetic controls were studied with the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction which detects preferentially apoptotic DNA fragmentation. The count of total TUNEL+ nuclei was significantly greater in the microvessels of diabetic (13 +/- 12 per one-sixth of retina) than control subjects (1.3 +/- 1.4, P = 0.0016), as were the counts of TUNEL+ pericytes and endothelial cells (P < 0.006). The neural retinas from both diabetic and nondiabetic subjects were uniformly TUNEL-. Retinal microvessels of rats with short duration of experimental diabetes or galactosemia and absent or minimal morphological changes of retinopathy, showed TUNEL+ pericytes and endothelial cells, which were absent in control rats. These findings indicate that (a) diabetes and galactosemia lead to accelerated death in situ of both retinal pericytes and endothelial cells; (b) the event is specific for vascular cells; (c) it precedes histological evidence of retinopathy; and (d) it can be induced by isolated hyperhexosemia. A cycle of accelerated death and renewal of endothelial cells may contribute to vascular architectural changes and, upon exhaustion of replicative life span, to capillary obliteration.
Reducing homocysteine levels does not prevent stroke recurrence
Authors: Scott Gottlieb
Journal: BMJ (2004)

Among patients with a previous stroke, reducing levels of the amino acid homocysteine in the blood with high dose vitamin therapy does not reduce the risk of recurrent stroke.

Previous studies have shown an association between raised levels of total homocysteine and the risk of stroke and heart disease ( Stroke 2004;35:169-74). Folic acid, pyridoxine (vitamin B-6), and cobalamin (vitamin B-12) are known to reduce plasma homocysteine levels, but the effectiveness of homocysteine lowering therapy to reduce the risk of stroke has not been confirmed by randomised trials.

Dr James Toole of Wake …
Hospital admissions for drug and alcohol use in people aged under 45
Authors: Susan Williams, Matt Hickman, Alex Bottle, Paul Aylin
Journal: BMJ (2005)

The annual health and social costs of misuse of alcohol and illegal drugs in England and Wales are estimated to be nearly £20bn each.w1 w2About 5.9 million people drink twice the recommended weekly consumption; 1 million people use ecstasy, cocaine, or other class A drugs each year; and more than 100 000 people are injecting drug users.w1 w3 w4Both alcohol and other problem drug use are associated with a range of harms and cause substantial morbidity and mortality.w1 w5 w6Trends in emergency room use have been used to indicate the level of harm in the population.w3 w4In the absence of accident and emergency data in England and Wales, we investigated trends in drug and alcohol related hospital admissions for people aged under 45. The bottom line
Thiazide Diuretics in the Treatment of Hypertension
Authors: Antonio Salvetti, Lorenzo Ghiadoni
Journal: Journal of the American Society of Nephrology (2006)

Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients, the following considerations should be taken into account. Although there are some indications that chlorthalidone can offer additional advantages as compared with other compounds, a recent meta-analysis of placebo-controlled trials suggested that the beneficial effects of thiazide diuretics could be a class effect. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with beta blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes, in whom thiazide diuretics should be used at the lowest active dose and possibly in combination with drugs that block the renin-angiotensin system. Finally, the current debate on whether thiazide diuretics are the first-choice drug for most patients with uncomplicated hypertension, as stated in the Seventh Joint National Committee Report, or are included in the major classes of antihypertensive agents that are suitable for initiation and maintenance of therapy, as reported in the European Society of Hypertension-European Society of Cardiology Guidelines, derives from different interpretations of controlled clinical trial data on drug class comparison and of cost-benefit analyses. However, considering that the benefit of antihypertensive drugs seems to be due principally to BP lowering per se without definitive evidence of the superiority of a particular drug class and that there is no cost-benefit analysis showing the superiority of thiazide diuretics, it is believed that these drugs should not be considered as the only first-choice drug but included among first-choice drugs.