tbuckley/cabot-search huggingface dataset:
Early curettage of giant congenital naevi in children
Authors: None Casanova, None Bardot, None Andrac‐Meyer, None Magalon
Journal: British Journal of Dermatology (1998)

Early curettage of giant congenital naevi in new‐born infants, if performed during the first few weeks after birth, can have a substantial effect on the pigmentation of the lesions, reducing the number of pigmented cells and leaving only moderate scars. We describe our experience in a series of nine congenital naevi treated by curettage between the first and seventh week after birth. Histological changes that occur in the naevus during the first few days after birth mean that early treatment is needed to obtain a cosmetic improvement. Curettage as an early treatment for giant congenital naevi in new‐born infants provides cosmetic improvement and might decrease the risk of malignancy; however, the lesions are not cured. Naevus cells persist in the deep dermal layers and may come to the surface, such that close monitoring is needed long after curettage. The cosmetic improvement is likely to benefit the child's psychological development.
Global Coronary Heart Disease Risk Assessment of Individuals With the Metabolic Syndrome in the U.S.
Authors: Khiet C. Hoang, Heli Ghandehari, Victor A. Lopez, Michael G. Barboza, Nathan D. Wong
Journal: Diabetes Care (2008)

Although metabolic syndrome is related to an increased risk of coronary heart disease (CHD) events, individuals with metabolic syndrome encompass a wide range of CHD risk levels. This study describes the distribution of 10-year CHD risk among U.S. adults with metabolic syndrome.Metabolic syndrome was defined by the modified National Cholesterol Education Program (NCEP)/Third Adult Treatment Panel (ATP III) definition among 4,293 U.S. adults aged 20-79 years in the National Health and Nutrition Examination Survey 2003-2004. Low-, moderate-, moderately high-, and high-risk statuses were defined as <6, 6 to <10, 10-20, and >20% probability of CHD in 10 years (based on NCEP/ATP III Framingham risk score algorithms), respectively; those with diabetes or preexisting cardiovascular disease were assigned to high-risk status.The weighted prevalence of metabolic syndrome by NCEP criteria in our study was 29.0% overall (30.0% in men and 27.9% in women, P = 0.28): 38.5% (30.7% men and 46.9% women) were classified as low risk, 8.5% (7.9% men and 9.1% women) were classified as moderate risk, 15.8% (23.4% men and 7.6% women) were classified as moderately high risk, and 37.3% (38.0% men and 36.5% women) were classified as high risk. The proportion at high risk increased with age but was similar among Hispanics, non-Hispanic whites, and non-Hispanic blacks.Although many subjects with metabolic syndrome have a low calculated risk for CHD, about half have a moderately high or high risk, reinforcing the need for global risk assessment in individuals with metabolic syndrome to appropriately target intensity of treatment for underlying CHD risk factors.
Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs
Authors: S. Stevens Negus, Laurence L. Miller
Journal: Pharmacological Reviews (2014)

Intracranial self-stimulation (ICSS) is a behavioral procedure in which operant responding is maintained by pulses of electrical brain stimulation. In research to study abuse-related drug effects, ICSS relies on electrode placements that target the medial forebrain bundle at the level of the lateral hypothalamus, and experimental sessions manipulate frequency or amplitude of stimulation to engender a wide range of baseline response rates or response probabilities. Under these conditions, drug-induced increases in low rates/probabilities of responding maintained by low frequencies/amplitudes of stimulation are interpreted as an abuse-related effect. Conversely, drug-induced decreases in high rates/probabilities of responding maintained by high frequencies/amplitudes of stimulation can be interpreted as an abuse-limiting effect. Overall abuse potential can be inferred from the relative expression of abuse-related and abuse-limiting effects. The sensitivity and selectivity of ICSS to detect abuse potential of many classes of abused drugs is similar to the sensitivity and selectivity of drug self-administration procedures. Moreover, similar to progressive-ratio drug self-administration procedures, ICSS data can be used to rank the relative abuse potential of different drugs. Strengths of ICSS in comparison with drug self-administration include 1) potential for simultaneous evaluation of both abuse-related and abuse-limiting effects, 2) flexibility for use with various routes of drug administration or drug vehicles, 3) utility for studies in drug-naive subjects as well as in subjects with controlled levels of prior drug exposure, and 4) utility for studies of drug time course. Taken together, these considerations suggest that ICSS can make significant contributions to the practice of abuse potential testing.
Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial
Authors: Valentino Conter, Maria Grazia Valsecchi, Daniela Silvestri, Myriam Campbell, Eduardo Dibar, Edina Magyarosy, Helmut Gadner, Jan Stary, Yves Benoit, Martin Zimmermann, Alfred Reiter, Hansjörg Riehm, Giuseppe Masera, Martin Schrappe
Journal: The Lancet (2007)
Atrial Fibrillation: Natural History, Complications, and Management
Authors: Joseph S. Alpert, Palle Petersen, John Godtfredsen
Journal: Annual Review of Medicine (1988)

Atrial fibrillation is a clinically important arrhythmia that carries important prognostic and therapeutic implications. Hypertension, ischemic heart disease, and rheumatic valvular disease are the commonest causes of atrial fibrillation. The presence of chronic or paroxysmal atrial fibrillation places the patient at increased risk for embolic stroke and/or death. When atrial fibrillation develops, there is loss of the atrial transport factor (“atrial kick”), with consequent decrease of cardiac output. Stroke output declines by 20-30% in normal individuals with loss of atrial kick; the decline in stroke output is considerably larger in patients with heart disease. Atrial fibrillation can be electrically or pharmacologically reverted to sinus rhythm. Even patients with refractory atrial fibrillation can be reverted to sinus rhythm with amiodarone.
Of SMN in mice and men: a therapeutic opportunity
Authors: Kathryn J. Swoboda
Journal: Journal of Clinical Investigation (2011)

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that predominantly affects motor neurons, resulting in progressive muscular atrophy and weakness. SMA arises due to insufficient survival motor neuron (SMN) protein levels as a result of homozygous disruption of the SMN1 gene. SMN upregulation is a promising and potent treatment strategy for this currently incurable condition. In this issue of the JCI, two independent research groups report novel observations in mouse models of severe SMA that provide hope that this approach will afford meaningful benefit to individuals with SMA.
Influence of the Polymorphisms Tpr64Arg in the β3-Adrenergic Receptor Gene and Pro12Ala in the PPARγ2 Gene on Metabolic Syndrome-Related Phenotypes in an Indigenous Population of the Brazilian Amazon
Authors: João Paulo B. Vieira-Filho, André F. Reis, Teresa S. Kasamatsu, Edelweiss F. Tavares, Laércio J. Franco, Sergio R. Matioli, Regina S. Moisés
Journal: Diabetes Care (2004)

Metabolic syndrome is a cluster of risk factors for type 2 diabetes and cardiovascular disease. Multiple mechanisms, including genetic factors, may contribute to this condition. The Trp64Arg variant in the β3-adrenergic receptor has been associated with features of the metabolic syndrome (1). A relatively common gene variant, Pro12Ala of the peroxisome proliferator-activated receptor-γ2 (PPARγ2) has been previously studied for association with obesity and type 2 diabetes (2,3).

The Parkataje Indians, from the Brazilian Amazon region, remained largely isolated. Recently, they underwent a rapid and intensive process of acculturation, with important changes in their lifestyle. Accompanying these changes, an increasing prevalence of obesity and other features of the metabolic syndrome have …
Deacetylase inhibition promotes the generation and function of regulatory T cells
Authors: Ran Tao, Edwin F de Zoeten, Engin Özkaynak, Chunxia Chen, Liqing Wang, Paige M Porrett, Bin Li, Laurence A Turka, Eric N Olson, Mark I Greene, Andrew D Wells, Wayne W Hancock
Journal: Nature Medicine (2007)
Epstein-Barr Virus As a Marker of Survival After Hodgkin's Lymphoma: A Population-Based Study
Authors: Theresa H.M. Keegan, Sally L. Glaser, Christina A. Clarke, Margaret L. Gulley, Fiona E. Craig, Joseph A. DiGiuseppe, Ronald F. Dorfman, Risa B. Mann, Richard F. Ambinder
Journal: Journal of Clinical Oncology (2005)

Epstein-Barr virus (EBV) in Hodgkin's lymphoma (HL) cells has been considered as a prognostic marker for this heterogeneous disease, but studies have yielded mixed findings, likely because of selected patient series and failure to acknowledge an effect of age on outcome. This study assessed survival after HL in a population-based cohort large enough to examine the joint effects of EBV with other factors including age, sex, and histologic subtype.Included were 922 patients with classical HL diagnosed between mid-1988 and 1997 in the Greater San Francisco Bay Area, with archived biopsy specimens assayed for EBV with immunohistochemistry and in situ hybridization. Vital status was followed through December 30, 2003 (median follow-up time, 97 months). Overall and disease-specific survival were analyzed with the Kaplan-Meier method and Cox proportional hazards regression models.In children less than 15 years old, EBV presence was suggestively associated (P = .07) with favorable survival. In adults aged 15 to 44 years, EBV did not affect HL outcome, although a protective effect was suggested. In older adults (45 to 96 years), EBV presence nearly doubled the risk of overall and HL-specific mortality but only for patients with nodular sclerosis (NS) histologic subtype (hazard ratio for death = 2.5; 95% CI, 1.5 to 4.3).In HL, EBV tumor cell presence is associated with better survival in young patients and poorer survival in older patients with NS, independent of other factors. Variation in outcome by age and histology could indicate biologically distinct disease entities. Evidence that EBV is a meaningful prognostic marker may have therapeutic relevance.
Effect of intra-articular corticosteroid injections and inflammation on periarticular and generalised bone loss in early rheumatoid arthritis
Authors: G. Haugeberg, S. Morton, P. Emery, P. G. Conaghan
Journal: Annals of the Rheumatic Diseases (2010)

To explore the effect of intra-articular corticosteroid (IAST) injections on bone mineral density (BMD) in the hand and at the metacarpophalangeal (MCP) joints in early rheumatoid arthritis (RA).In the first 3 months of the study, 19 patients with RA received methotrexate (MTX) alone and 21 received MTX and IAST injections into clinically inflamed joints. In the following 9 months, all patients received MTX+IAST. BMD was assessed at the hand and periarticular regions at MCP joints 2-5 at baseline, 3 and 12 months.In the first 3 months a numerically lower percentage rate of bone loss was seen in MTX+IAST-treated patients compared with MTX-treated patients. This observation was more pronounced at the MCP periarticular regions (eg, partial proximal phalanges: digit 2, -0.45% vs -2.69%, p=0.045; digit 3, -0.34% vs -3.32%, p=0.003; digit 4, -0.39% vs -2.57%, p=0.14; digit 5, -0.59% vs -2.70%, p=0.24) than for the whole hand (-1.53% vs -2.42%, p=0.32). In the 3-12-month period, only minor non-statistically significant differences were seen between the two groups.IAST given over 3 months protects against periarticular bone loss in inflamed finger joints in RA. These data emphasise the importance of suppressing inflammation in patients with active RA to maintain bone health.
Small Molecule Targeting the Hec1/Nek2 Mitotic Pathway Suppresses Tumor Cell Growth in Culture and in Animal
Authors: Guikai Wu, Xiao-Long Qiu, Longen Zhou, Jiewen Zhu, Richard Chamberlin, Johnson Lau, Phang-Lang Chen, Wen-Hwa Lee
Journal: Cancer Research (2008)

Abstract Hec1 is a conserved mitotic regulator critical for spindle checkpoint control, kinetochore functionality, and cell survival. Overexpression of Hec1 has been detected in a variety of human cancers and is linked to poor prognosis of primary breast cancers. Through a chemical genetic screening, we have identified a small molecule, N-(4-[2,4-dimethyl-phenyl]-thiazol-2-yl)-benzamide (INH1), which specifically disrupts the Hec1/Nek2 interaction via direct Hec1 binding. Treating cells with INH1 triggered reduction of kinetochore-bound Hec1 as well as global Nek2 protein level, consequently leading to metaphase chromosome misalignment, spindle aberrancy, and eventual cell death. INH1 effectively inhibited the proliferation of multiple human breast cancer cell lines in culture (GI50, 10–21 μmol/L). Furthermore, treatment with INH1 retarded tumor growth in a nude mouse model bearing xenografts derived from the human breast cancer line MDA-MB-468, with no apparent side effects. This study suggests that the Hec1/Nek2 pathway may serve as a novel mitotic target for cancer intervention by small compounds. [Cancer Res 2008;68(20):8393–9]
The Devil in the Details: Thorough Assessment of Evidence and Ethics Is Needed in Evaluating New HIV Prevention Methods
Authors: Liza Dawson
Journal: The American Journal of Bioethics (2012)

Click to increase image sizeClick to decrease image size Acknowledgments This article is not subject to U.S. Copyright Law. The views expressed are those of the author, and do not represent the views or policies of the US Department of Health and Human Services, or of the National Institutes of Health, National Institute of Allergy and Infectious Diseases.
The RL-ET-14 cell line mediates expression of glutamine synthetase through the upstream enhancer/promoter region
Authors: Marianna Kruithof-de Julio, Wilhelmina T. Labruyère, Jan M. Ruijter, Jacqueline L.M. Vermeulen, Vesna Stanulović, Jan M.P. Stallen, Alicja Baldysiak-Figiel, Rolf Gebhardt, Wouter H. Lamers, Theodorus B.M. Hakvoort
Journal: Journal of Hepatology (2005)
Late Referrals to Specialized Palliative Care Service in Japan
Authors: Tatsuya Morita, Tatsuo Akechi, Masayuki Ikenaga, Yoshiyuki Kizawa, Hiroyuki Kohara, Taketo Mukaiyama, Toshimichi Nakaho, Nobuaki Nakashima, Yasuo Shima, Tatsuhiro Matsubara, Yosuke Uchitomi
Journal: Journal of Clinical Oncology (2005)

Purpose To clarify the bereaved family's perceptions about the appropriateness of timing when physicians first referred patients to palliative care units, and to identify the factors contributing to family-perceived late referrals. Subjects and Methods A multicenter questionnaire survey was conducted on 630 bereaved family members of cancer patents who were admitted to palliative care units in Japan. A total of 318 responses were analyzed (effective response rate, 62%). Results Half of the bereaved family members regarded the timing of referrals to palliative care units as late or very late, while less than 5% of families reported early referrals (very late [19%, n = 59], late [30%, n = 96], appropriate [48%, n = 151], early [1.6%, n = 5], and very early [2.2%, n = 7]). Multiple regression analyses revealed that the independent determinants of family-perceived late referrals were: family belief before admission that palliative care shortens the patient's life, insufficient in-advance discussion about preferred end-of-life care between patients/families and physicians, families' insufficient preparation for changes of patient conditions, and hospital admission before referrals. Conclusion In Japan, the timing of referrals to palliative care units was late or very late from the families' perspectives. The independent determinants of family-perceived late referrals were: family misconception about palliative care, inadequate communication with physicians, and families' insufficient preparation for deterioration of patients' conditions. Systematic strategies to overcome these barriers would contribute to providing appropriate palliative care at all stages of cancer.
Left Ventricular Volume Studies in Tranquilized Dogs with Local Anesthesia
Authors: J. David Bristow, Cyrus Farrehi, Kent Ueland
Journal: Circulation Research (1966)

Left ventricular volumes were estimated by thermodilution in unanesthetized dogs given the tranquilizer, perphenazine. During systole, the left ventricle emptied an average of 40% of its end-diastolic volume. This is a significantly greater proportion than observed previously during general anesthesia with several different agents. Left ventricular mid-systolic wall force was calculated. Higher force values at a given end-diastolic volume occurred during intravenous infusion of norepinephrine. Methoxamine failed to change these relationships.
Bicc1 is a genetic determinant of osteoblastogenesis and bone mineral density
Authors: Larry D. Mesner, Brianne Ray, Yi-Hsiang Hsu, Ani Manichaikul, Eric Lum, Elizabeth C. Bryda, Stephen S. Rich, Clifford J. Rosen, Michael H. Criqui, Matthew Allison, Matthew J. Budoff, Thomas L. Clemens, Charles R. Farber
Journal: Journal of Clinical Investigation (2014)

Patient bone mineral density (BMD) predicts the likelihood of osteoporotic fracture. While substantial progress has been made toward elucidating the genetic determinants of BMD, our understanding of the factors involved remains incomplete. Here, using a systems genetics approach in the mouse, we predicted that bicaudal C homolog 1 (Bicc1), which encodes an RNA-binding protein, is responsible for a BMD quantitative trait locus (QTL) located on murine chromosome 10. Consistent with this prediction, mice heterozygous for a null allele of Bicc1 had low BMD. We used a coexpression network–based approach to determine how Bicc1 influences BMD. Based on this analysis, we inferred that Bicc1 was involved in osteoblast differentiation and that polycystic kidney disease 2 (Pkd2) was a downstream target of Bicc1. Knock down of Bicc1 and Pkd2 impaired osteoblastogenesis, and Bicc1 deficiency–dependent osteoblast defects were rescued by Pkd2 overexpression. Last, in 2 human BMD genome-wide association (GWAS) meta-analyses, we identified SNPs in BICC1 and PKD2 that were associated with BMD. These results, in both mice and humans, identify Bicc1 as a genetic determinant of osteoblastogenesis and BMD and suggest that it does so by regulating Pkd2 transcript levels.
Complete mtDNA Sequences of Two Millipedes Suggest a New Model for Mitochondrial Gene Rearrangements: Duplication and Nonrandom Loss
Authors: Dennis V. Lavrov, Jeffrey L. Boore, Wesley M. Brown
Journal: Molecular Biology and Evolution (2002)

We determined the complete mitochondrial DNA (mtDNA) sequences of the millipedes Narceus annularus and Thyropygus sp. (Arthropoda: Diplopoda) and identified, in both genomes, all 37 genes typical for metazoan mtDNA. The arrangement of these genes is identical in the two millipedes, but differs from others found in arthropod mtDNAs in the location of at least four genes or gene blocks. This novel gene arrangement is unusual for animal mtDNA in that genes with identical transcriptional polarities are clustered in the genome, and the two clusters are separated by two noncoding regions. The only exception to this pattern is the gene for cysteine tRNA, which is located in the part of the genome that otherwise contains all genes with the opposite transcriptional polarity. We suggest that a mechanism involving complete mtDNA duplication followed by the loss of genes, predetermined by their transcriptional polarity and location in the genome, could generate this gene arrangement from the one ancestral for arthropods. The proposed mechanism has important implications for phylogenetic inferences that are drawn on the basis of gene arrangement comparisons.
Purinergic Signaling in the Airways
Authors: Geoffrey Burnstock, Inge Brouns, Dirk Adriaensen, Jean-Pierre Timmermans
Journal: Pharmacological Reviews (2012)

Evidence for a significant role and impact of purinergic signaling in normal and diseased airways is now beyond dispute. The present review intends to provide the current state of knowledge of the involvement of purinergic pathways in the upper and lower airways and lungs, thereby differentiating the involvement of different tissues, such as the epithelial lining, immune cells, airway smooth muscle, vasculature, peripheral and central innervation, and neuroendocrine system. In addition to the vast number of well illustrated functions for purinergic signaling in the healthy respiratory tract, increasing data pointing to enhanced levels of ATP and/or adenosine in airway secretions of patients with airway damage and respiratory diseases corroborates the emerging view that purines act as clinically important mediators resulting in either proinflammatory or protective responses. Purinergic signaling has been implicated in lung injury and in the pathogenesis of a wide range of respiratory disorders and diseases, including asthma, chronic obstructive pulmonary disease, inflammation, cystic fibrosis, lung cancer, and pulmonary hypertension. These ostensibly enigmatic actions are based on widely different mechanisms, which are influenced by the cellular microenvironment, but especially the subtypes of purine receptors involved and the activity of distinct members of the ectonucleotidase family, the latter being potential protein targets for therapeutic implementation.
Time Trends in Brain Tumor Incidence Rates in Denmark, Finland, Norway, and Sweden, 1974-2003
Authors: I. Deltour, C. Johansen, A. Auvinen, M. Feychting, L. Klaeboe, J. Schuz
Journal: JNCI Journal of the National Cancer Institute (2009)

In Denmark, Finland, Norway, and Sweden, the use of mobile phones increased sharply in the mid-1990s; thus, time trends in brain tumor incidence after 1998 may provide information about possible tumor risks associated with mobile phone use. We investigated time trends in the incidence of glioma and meningioma in Denmark, Finland, Norway, and Sweden from 1974 to 2003, using data from national cancer registries. We used joinpoint regression models to analyze the annual incidence rates of glioma and meningioma. During this period, 59,984 men and women aged 20-79 years were diagnosed with brain tumors in a population of 16 million adults. All statistical tests were two-sided. From 1974 to 2003, the incidence rate of glioma increased by 0.5% per year (95% confidence interval [CI] = 0.2% to 0.8%) among men and by 0.2% per year (95% CI = -0.1% to 0.5%) among women and that of meningioma increased by 0.8% per year (95% CI = 0.4% to 1.3%) among men, and after the early 1990s, by 3.8% per year (95% CI = 3.2% to 4.4%) among women. No change in incidence trends were observed from 1998 to 2003, the time when possible associations between mobile phone use and cancer risk would be informative about an induction period of 5-10 years.