tbuckley/cabot-search huggingface dataset:
Impact of<i>in vivo</i>reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions
Authors: I. Alarcon, C. Carrera, J. Palou, L. Alos, J. Malvehy, S. Puig
Journal: British Journal of Dermatology (2013)

Journal Article Impact of in vivo reflectance confocal microscopy on the number needed to treat melanoma in doubtful lesions Get access I. Alarcon, I. Alarcon Dermatology Department Melanoma Unit Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) Villarroel 170 Barcelona 08036 Spain Search for other works by this author on: Oxford Academic Google Scholar C. Carrera, C. Carrera Dermatology Department Melanoma Unit Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) Villarroel 170 Barcelona 08036 SpainCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) Barcelona Spain Search for other works by this author on: Oxford Academic Google Scholar J. Palou, J. Palou Department of Pathology Hospital Clinic of Barcelona Barcelona Spain Search for other works by this author on: Oxford Academic Google Scholar L. Alos, L. Alos Department of Pathology Hospital Clinic of Barcelona Barcelona Spain Search for other works by this author on: Oxford Academic Google Scholar J. Malvehy, J. Malvehy Dermatology Department Melanoma Unit Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) Villarroel 170 Barcelona 08036 SpainCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) Barcelona Spain Search for other works by this author on: Oxford Academic Google Scholar S. Puig S. Puig Dermatology Department Melanoma Unit Hospital Clinic & IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer) Villarroel 170 Barcelona 08036 SpainCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) Barcelona SpainDepartment of Medicine University of Barcelona Barcelona Spain Correspondence Susana Puig. E‐mail: susipuig@gmail.com; spuig@clinic.ub.es Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 170, Issue 4, 1 April 2014, Pages 802–808, https://doi.org/10.1111/bjd.12678 Published: 01 April 2014
A 60-Year-Old Woman With Mild Memory Impairment
Authors: James M. Ellison
Journal: JAMA (2008)

Many older individuals experience or demonstrate cognitive impairment that is significantly abnormal for their age and education yet beneath the threshold for a diagnosis of dementia. This mild cognitive impairment causes minimal functional impairment and is often overlooked in clinical settings, yet affected individuals are at heightened risk for a range of adverse outcomes including conversion to dementia. The case of Ms E, a 60-year-old woman with mild memory impairment and white matter lesions on magnetic resonance imaging, provides an opportunity to consider the questions that face patient, family, and clinicians when mild cognitive symptoms prompt a search for diagnosis and management options. Discussion of her case reviews mild cognitive impairment with emphasis on an evidence-based approach to evaluation and treatment, including management of comorbid medical conditions, lifestyle changes, and pharmacotherapy.
Family History of Premature Coronary Heart Disease and Coronary Artery Calcification
Authors: Khurram Nasir, Matthew J. Budoff, Nathan D. Wong, Maren Scheuner, David Herrington, Donna K. Arnett, Moyses Szklo, Philip Greenland, Roger S. Blumenthal
Journal: Circulation (2007)

Background— A family history of premature coronary heart disease (CHD) is a known risk factor for CHD events. The purpose of this study was to assess the strength of the association between a family history of premature CHD and coronary artery calcification (CAC) in a multiethnic cohort of asymptomatic individuals. We also sought to determine whether individuals with a reported family history of premature CHD have an increased atherosclerotic burden among those classified as being at low to intermediate risk on the basis of the conventional Framingham risk score. Methods and Results— The association of family history of premature CHD with CAC was assessed in 5347 asymptomatic individuals (47% men; mean age 62±10 years) in the Multi-Ethnic Study of Atherosclerosis (MESA). The demographics (age, gender, and race)–adjusted OR for CAC &gt;0 with versus without a family history of premature CHD was 1.94 (95% CI, 1.64 to 2.29). On adjustment for CHD risk factors, the association was slightly attenuated to an OR of 1.84 (95% CI, 1.55 to 2.19). Family history of premature CHD was significantly associated with CAC in all ethnic groups. The age-, gender-, and race-adjusted prevalence of CAC &gt;0 was significantly higher with presence of any family history of premature CHD than for those with no family history of premature CHD among individuals classified as low risk (35% versus 23%, P &lt;0.0001) and among those at intermediate risk (70% versus 60%, P =0.01). Similarly, the prevalence of age-gender-race–based CAC ≥75th percentile in low-risk (24% versus 14%, P =0.0003) and intermediate-risk (34% versus 20%, P &lt;0.001) individuals was also higher among those with a family history of premature CHD. Compared with those without a family history of premature CHD, the association with the presence of CAC was strongest in participants reporting such history in both a parent and a sibling (odds ratio, 2.74; 95% CI, 1.64 to 4.59), followed by those reporting a family history in a sibling only (odds ratio, 2.06; 95% CI, 1.64 to 2.58) and those reporting a family history of premature CHD only in a parent (odds ratio, 1.52; 95% CI, 1.19 to 1.93). Conclusions— An association between family history of premature CHD and the presence of any CAC, as well as advanced CAC, was observed in the present population-based multiethnic study. The relationship was independent of other risk factors and Framingham risk score, which supports the utility of including information on family history of premature CHD in current methods of global risk assessment and practice guidelines.
Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function
Authors: Maxim Ivanov, Mart Kals, Marina Kacevska, Isabel Barragan, Kie Kasuga, Anders Rane, Andres Metspalu, Lili Milani, Magnus Ingelman-Sundberg
Journal: Genome biology (2013)

Abstract Background Interindividual differences in liver functions such as protein synthesis, lipid and carbohydrate metabolism and drug metabolism are influenced by epigenetic factors. The role of the epigenetic machinery in such processes has, however, been barely investigated. 5-hydroxymethylcytosine (5hmC) is a recently re-discovered epigenetic DNA modification that plays an important role in the control of gene expression. Results In this study, we investigate 5hmC occurrence and genomic distribution in 8 fetal and 7 adult human liver samples in relation to ontogeny and function. LC-MS analysis shows that in the adult liver samples 5hmC comprises up to 1% of the total cytosine content, whereas in all fetal livers it is below 0.125%. Immunohistostaining of liver sections with a polyclonal anti-5hmC antibody shows that 5hmC is detected in most of the hepatocytes. Genome-wide mapping of the distribution of 5hmC in human liver samples by next-generation sequencing shows significant differences between fetal and adult livers. In adult livers, 5hmC occupancy is overrepresented in genes involved in active catabolic and metabolic processes, whereas 5hmC elements which are found in genes exclusively in fetal livers and disappear in the adult state, are more specific to pathways for differentiation and development. Conclusions Our findings suggest that 5-hydroxymethylcytosine plays an important role in the development and function of the human liver and might be an important determinant for development of liver diseases as well as of the interindividual differences in drug metabolism and toxicity.
Evidence for an Intrinsic Renal Tubular Defect in Mice with Genetic Hypophosphatemic Rickets
Authors: Larry D. Cowgill, Stanley Goldfarb, Kai Lau, Eduardo Slatopolsky, Zalman S. Agus
Journal: Journal of Clinical Investigation (1979)

To investigate the role of parathyroid hormone (PTH) and(or) an intrinsic renal tubular reabsorptive defect for phosphate in mice with hereditary hypophosphatemic rickets, we performed clearance and micropuncture studies in hypophosphatemic mutants and nonaffected littermate controls. Increased fractional excretion of phosphate in mutants (47.2+/-4 vs. 30.8+/-2% in controls) was associated with reduced fractional and absolute reabsorption in the proximal convoluted tubule and more distal sites. Acute thyropara-thyroidectomy (TPTX) increased phosphate reabsorption in both mutants and controls with a fall in fractional phosphate excretion to congruent with7.5% in both groups indicating that PTH modified the degree of phosphaturia in the intact mutants. Absolute reabsorption in the proximal tubule and beyond remained reduced in the mutants, however, possibly because of the reduced filtered load. Serum PTH levels were the same in intact mutants and normals as was renal cortical adenylate cyclase activity both before and after PTH stimulation. To evaluate the possibility that the phosphate wasting was caused by an intrinsic tubular defect that was masked by TPTX, glomerular fluid phosphate concentration was raised by phosphate infusion in TPTX mutants to levels approaching those of control mice. Phosphate excretion rose markedly and fractional reabsorption fell, but there was no change in absolute phosphate reabsorption in either the proximal tubule or beyond, indicating a persistent reabsorptive defect in the absence of PTH. We conclude that hereditary hypophosphatemia in the mouse is associated with a renal tubular defect in phosphate reabsorption, which is independent of PTH and therefore represents a specific intrinsic abnormality of phosphate transport.
cGMP and Atrial Natriuretic Factor Regulate Cell Volume of Rabbit Atrial Myocytes
Authors: Henry F. Clemo, Clive Marc Baumgarten
Journal: Circulation Research (1995)

Abstract Atrial natriuretic factor (ANF) reduces the volume of atrial myocytes by inhibiting Na + /K + /2Cl − cotransport. We determined the role of cGMP and cAMP in ANF-induced shrinkage by using digital video microscopy to measure cell volume; volumes are reported relative to control. ANF (1 μmol/L) reversibly reduced atrial cell volume from 1.0 to 0.915±0.005 (mean±SEM). This effect was mimicked by 10 μmol/L 8-bromo-cGMP (8-Br-cGMP), which decreased myocyte volume to 0.894±0.007 with an ED 50 of 0.99±0.05 μmol/L. In contrast, 100 μmol/L 8-bromo-cAMP (8-Br-cAMP) did not affect volume, and activating the cAMP pathway with 100 μmol/L 8-Br-cAMP did not alter the volume decrease caused by 8-Br-cGMP or ANF. Inhibition of Na + /K + /2Cl − cotransport with bumetanide (1 μmol/L) also reduced cell volume and prevented further shrinkage on subsequent exposure to 8-Br-cGMP. Similarly, 8-Br-cGMP (10 μmol/L) prevented further shrinkage by ANF. Block of Na + -H + exchange, a participant in volume regulation in other cells, did not alter the response to 8-Br-cGMP. More evidence implicating cGMP was obtained by altering its metabolism. LY83583 (10 μmol/L), a guanylate cyclase inhibitor, blocked ANF-induced cell shrinkage. Zaprinast (100 μmol/L), a cGMP-specific phosphodiesterase inhibitor, markedly potentiated the effect of a threshold concentration of ANF (0.01 μmol/L). The actions of ANF, LY83583, and zaprinast on cGMP levels were verified by radioimmunoassay. These data strongly support the idea that the cGMP cascade is the intracellular signaling pathway responsible for ANF-induced atrial cell shrinkage. ANF activates guanylate cyclase, and the subsequent rise in cGMP inhibits Na + /K + /2Cl − cotransport. This reduces the uptake of osmolytes, and cell shrinkage follows. In addition, LY83583 caused a small swelling and zaprinast caused a small shrinkage in the absence of other agents. This suggests that physiological levels of cGMP partially inhibit Na + /K + /2Cl − cotransport and help set isosmotic cell volume. It is proposed that ANF-induced elevation of atrial cGMP and the ensuing cell shrinkage serve as a negative-feedback mechanism limiting stretch-induced ANF secretion.
Needle Biopsy for Breast Cancer Diagnosis: A Quality Metric for Breast Surgical Practice
Authors: Kristine E. Calhoun, Benjamin O. Anderson
Journal: Journal of Clinical Oncology (2014)

Thus,PNBrepresentsanimportant transition in breast cancer management of speciﬁc in-terest to surgeons.Surgical biopsy was the “gold standard” for breast diagnosisbefore the early 1990s, when most patients with breast cancerpresentedwithclinicalsymptomsandwerereferredtosurgeonsfordiagnostic work-up. The growth in the rate of mammographicscreening in the 1980s signiﬁcantly increased the number of non-palpable breast lesions that required diagnostic work-up. Im-proved methods for tissue sampling were needed to alleviate thegrowing numbers of surgical biopsies that require cumbersomewire localization operations and to simplify biopsy of palpablelesions in the ofﬁce using only local anesthetic.Fine needle aspiration biopsy (FNAB) was the ﬁrst percutaneousneedle sampling technique introduced as an alternative to surgical exci-sional or incisional biopsy.
Money, play, and instincts
Authors: Gordon M. Burghardt
Journal: Behavioral and Brain Sciences (2006)

The metaphor drug model of money slights the possibility that money may literally tap into and exploit brain systems underlying motivational systems, and it also ignores growing evidence on the common neural substrates of behavioral and “physiological” addictions. Additionally, many objects other than money can gain such drug-like properties. The treatment of play in the evolutionary explanation for the unique role of money in people ignores key conceptual and empirical issues.
Altered expression of the TCR signaling related genes CD3 and FcεRIγ in patients with aplastic anemia
Authors: Bo Li, Sichu Liu, Yuzhe Niu, Su Fang, Xiuli Wu, Zhi Yu, Shaohua Chen, Lijian Yang, Yangqiu Li
Journal: Journal of Hematology & Oncology (2012)

Aplastic anemia (AA) is characterized by pancytopenia and bone marrow hypoplasia, which results from immune-mediated hematopoiesis suppression. Understanding the pathophysiology of the immune system, particularly T cells immunity, has led to improved AA treatment over the past decades. However, primary and secondary failure after immunosuppressive therapy is frequent. Thus, knowledge of the immune mechanisms leading to AA is crucial to fundamentally understand the disease. To elucidate the T cell receptor (TCR) signal transduction features in AA, the expression levels of CD3γ, δ, ε and ζ chain and FcεRIγ genes, which are involved in TCR signal transduction, and the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes in T cells from peripheral blood mononuclear cells (PBMCs) were analyzed. Real-time RT-PCR using the SYBR Green method was used to detect the expression level of these genes in PBMCs from 18 patients with AA and 14 healthy individuals. The β2microglobulin gene (β2M) was used as an endogenous reference. The expression levels of the CD3γ, CD3δ, CD3ε and CD3ζ genes in patients with AA were significantly increased compared to a healthy control group, whereas the FcεRIγ gene expression level was significantly decreased in patients with AA in comparison with the healthy control group. Moreover, the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes was lost. To our knowledge, this is the first report of the CD3γ, CD3δ, CD3ε, CD3ζ and FcεRIγ gene expression in patients with AA. The abnormally expressed TCR signaling related genes may relate to T cells dysfunction in AA.
In vivo measurement of the keratolytic effect of salicylic acid in three ointment formulations
Authors: T.H. NOOK
Journal: British Journal of Dermatology (1987)

The release and activity of salicylic acid from different ointment formulations was studied in vivo by staining the horny layer with silver nitrate and measuring the light reflectance profile over 56 h, after application of the ointment for 4 h. The peeling effect of an ointment containing 5% salicylic acid and 10% urea was tested and compared with 5% and 10% salicylic acid in petrolatum. It was shown that shedding from the stained sites was faster with the urea containing preparation than with the classic petrolatum ointments. The method described can be used to assess the bioavailability of keratolytic agents incorporated in topical formulations.
Ductal Access for Prevention and Therapy of Mammary Tumors
Authors: Satoshi Murata, Scott L. Kominsky, Mustafa Vali, Zhe Zhang, Elizabeth Garrett-Mayer, Dorian Korz, David Huso, Sharyn D. Baker, James Barber, Elizabeth Jaffee, R. Todd Reilly, Saraswati Sukumar
Journal: Cancer Research (2006)

Abstract In cancer patients and in those at high risk, systemic exposure to agents for therapy or prevention is accompanied by undesirable side effects. We hypothesized that it is possible to prevent and treat breast cancer by introducing anticancer agents into the mammary ductal network. Here, we show the efficacy of intraductally administered anticancer agents 4-hydroxytamoxifen and pegylated liposomal doxorubicin (PLD) in the prevention and treatment of breast cancer using the rat N-methyl-N′-nitrosourea–induced and spontaneous HER-2/neu transgenic mouse (neu-N) models of breast cancer. Intraductal administration of PLD to neu-N mice caused regression of established tumors and prevented tumor development more effectively than i.v. injection (P &amp;lt; 0.0001). Intraductal administration resulted in lower circulating levels of PLD compared with i.v. administration, with no evidence of systemic toxicity or long-term histopathologic changes in the mammary gland. Compared with systemic administration, intraductal injection provides direct access to breast lesions with higher local and lower systemic drug exposure. These studies suggest that this approach has potential for application to prevention and neoadjuvant therapy of early breast cancer. (Cancer Res 2006; 66(2): 638-45)
WARD EPIDEMIC FROM NORWEGIAN SCABIES.
Authors: JOHN T. INGRAM
Journal: British Journal of Dermatology (1951)

Journal Article WARD EPIDEMIC FROM NORWEGIAN SCABIES. Get access JOHN T. INGRAM, M.D., F.R.C.P. JOHN T. INGRAM, M.D., F.R.C.P. Physician in Charge of the skin Department, General Infirmary, Leeds; Lecturer on Diseases of the Skin, University of Leeds Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 63, Issue 8-9, 1 August 1951, Pages 311–317, https://doi.org/10.1111/j.1365-2133.1951.tb13732.x Published: 01 August 1951
G-CSF/SCF reduces inducible arrhythmias in the infarcted heart potentially via increased connexin43 expression and arteriogenesis
Authors: Michael T. Kuhlmann, Paulus Kirchhof, Rainer Klocke, Lekbira Hasib, Jörg Stypmann, Larissa Fabritz, Matthias Stelljes, Wen Tian, Melanie Zwiener, Marcus Mueller, Joachim Kienast, Günter Breithardt, Sigrid Nikol
Journal: The Journal of Experimental Medicine (2006)

Granulocyte colony-stimulating factor (G-CSF), alone or in combination with stem cell factor (SCF), can improve hemodynamic cardiac function after myocardial infarction. Apart from impairing the pump function, myocardial infarction causes an enhanced vulnerability to ventricular arrhythmias. Therefore, we investigated the electrophysiological effects of G-CSF/SCF and the underlying cellular events in a murine infarction model. G-CSF/SCF improved cardiac output after myocardial infarction. Although G-CSF/SCF led to a twofold increased, potentially proarrhythmic homing of bone marrow (BM)-derived cells to the area of infarction, &amp;lt;1% of these cells adopted a cardial phenotype. Inducibility of ventricular tachycardias during programmed stimulation was reduced 5 wk after G-CSF/SCF treatment. G-CSF/SCF increased cardiomyocyte diameter, arteriogenesis, and expression of connexin43 in the border zone of the infarction. An enhanced expression of the G-CSF receptor demonstrated in cardiomyocytes and other cell types of the infarcted myocardium indicates a sensitization of the heart to direct influences of this cytokine. In addition to paracrine effects potentially caused by the increased homing of BM-derived cells, these might contribute to the therapeutic effects of G-CSF.
EU commissioner pursues smoking ban in enclosed public spaces for Europe
Authors: A. Tuffs
Journal: BMJ (2010)

<h3>ABSTRACT</h3> Spontaneous bursts of electrical activity in the developing auditory system arise within the cochlea prior to hearing onset and propagate through future sound processing circuits of the brain to promote maturation of auditory neurons. Studies in isolated cochleae revealed that this intrinsically generated activity is initiated by ATP release from inner supporting cells (ISCs), resulting in activation of purinergic autoreceptors, K<sup>+</sup> efflux and subsequent depolarization of inner hair cells (IHCs). However, little is known about when this activity emerges or whether different mechanisms underlie distinct stages of development. Here we show that spontaneous electrical activity in mouse cochlea emerges within ISCs during the late embryonic period, preceding the onset of spontaneous correlated activity in IHCs and spiral ganglion neurons (SGNs), which begins at birth and follows a base to apex developmental gradient. At all developmental stages, pharmacological inhibition of P2Y1 metabotropic purinergic receptors dramatically reduced spontaneous activity in these three cell types. Moreover, <i>in vivo</i> imaging within the inferior colliculus of awake mice revealed that auditory neurons within future isofrequency zones exhibit coordinated neural activity at birth. The frequency of these discrete bursts increased progressively during the postnatal prehearing period, yet remained dependent on P2RY1. Analysis of mice with disrupted cholinergic signaling in the cochlea, indicate that this input modulates, rather than initiates, spontaneous activity before hearing onset. Thus, the auditory system uses a consistent mechanism involving ATP release from ISCs and activation of purinergic autoreceptors to elicit coordinated excitation of neurons that will process similar frequencies of sound. <h3>SIGNIFICANCE STATEMENT</h3> In developing sensory systems, groups of neurons that will process information from similar sensory space exhibit highly correlated electrical activity that is critical for proper maturation and circuit refinement. Defining the period when this activity is present, the mechanisms responsible and the features of this activity are crucial for understanding how spontaneous activity influences circuit development. We show that, from birth to hearing onset, the auditory system relies on a consistent mechanism to elicit correlate firing of neurons that will process similar frequencies of sound. Targeted disruption of this activity will increase our understanding of how these early circuits mature and may provide insight into processes responsible for developmental disorders of the auditory system.