tbuckley/cabot-search huggingface dataset:
Familial melanoma: Clinical factors associated with germline CDKN2A mutations according to the number of patients affected by melanoma in a family
Authors: Eve Maubec, Valérie Chaudru, Hamida Mohamdi, Christophe Blondel, Patricia Margaritte-Jeannin, Sébastien Forget, Eve Corda, Françoise Boitier, Stéphane Dalle, Pierre Vabres, Jean-Luc Perrot, Dominique Stoppa Lyonnet, Hélène Zattara, Sandrine Mansard, Florent Grange, Marie-Thérèse Leccia, Lynda Vincent-Fetita, Ludovic Martin, Béatrice Crickx, Pascal Joly, Luc Thomas, Brigitte Bressac-de Paillerets, Marie-Françoise Avril, Florence Demenais
Journal: Journal of the American Academy of Dermatology (2012)
Genetics in Arterial Calcification
Authors: Frank Rutsch, Yvonne Nitschke, Robert Terkeltaub
Journal: Circulation Research (2011)

Artery calcification reflects an admixture of factors such as ectopic osteochondral differentiation with primary host pathological conditions. We review how genetic factors, as identified by human genome-wide association studies, and incomplete correlations with various mouse studies, including knockout and strain analyses, fit into “pieces of the puzzle” in intimal calcification in human atherosclerosis, and artery tunica media calcification in aging, diabetes mellitus, and chronic kidney disease. We also describe in sharp contrast how ENPP1, CD73, and ABCC6 serve as “cogs in a wheel” of arterial calcification. Specifically, each is a minor component in the function of a much larger network of factors that exert balanced effects to promote and suppress arterial calcification. For the network to normally suppress spontaneous arterial calcification, the “cogs” ENPP1, CD73, and ABCC6 must be present and in working order. Monogenic ENPP1, CD73, and ABCC6 deficiencies each drive a molecular pathophysiology of closely related but phenotypically different diseases (generalized arterial calcification of infancy (GACI), pseudoxanthoma elasticum (PXE) and arterial calcification caused by CD73 deficiency (ACDC)), in which premature onset arterial calcification is a prominent but not the sole feature.
Influence of Dose on Skin Tumors Induced in Mice by Single Application of 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene
Authors: V. Turusov, N. Day, L. Andrianov, D. Jain
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Influence of Dose on Skin Tumors Induced in Mice by Single Application of 7,12-Dimethylbenz[a]anthracene Get access V. Turusov, V. Turusov Institute of Experimental and Clinical Oncology, Moscow, USSR, and International Agency for Research on Cancer, Lyon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Day, N. Day Institute of Experimental and Clinical Oncology, Moscow, USSR, and International Agency for Research on Cancer, Lyon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Andrianov, L. Andrianov Institute of Experimental and Clinical Oncology, Moscow, USSR, and International Agency for Research on Cancer, Lyon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Jain D. Jain Institute of Experimental and Clinical Oncology, Moscow, USSR, and International Agency for Research on Cancer, Lyon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 47, Issue 1, July 1971, Pages 105–111, https://doi.org/10.1093/jnci/47.1.105 Published: 01 July 1971 Article history Received: 31 December 1970 Accepted: 07 April 1971 Published: 01 July 1971
Hydroxyurea induces fetal hemoglobin by the nitric oxide–dependent activation of soluble guanylyl cyclase
Authors: Vladan P. Cokic, Reginald D. Smith, Bojana B. Beleslin-Cokic, Joyce M. Njoroge, Jeffery L. Miller, Mark T. Gladwin, Alan N. Schechter
Journal: Journal of Clinical Investigation (2003)

Hydroxyurea treatment of patients with sickle-cell disease increases fetal hemoglobin (HbF), which reduces hemoglobin S polymerization and clinical complications. Despite its use in the treatment of myeloproliferative diseases for over 30 years, its mechanism of action remains uncertain. Recent studies have demonstrated that hydroxyurea generates the nitric oxide (NO) radical in vivo, and we therefore hypothesized that NO-donor properties might determine the hemoglobin phenotype. We treated both K562 erythroleukemic cells and human erythroid progenitor cells with S-nitrosocysteine (CysNO), an NO donor, and found similar dose- and time-dependent induction of γ-globin mRNA and HbF protein as we observed with hydroxyurea. Both hydroxyurea and CysNO increased cGMP levels, and the guanylyl cyclase inhibitors ODQ, NS 2028, and LY 83,538 abolished both the hydroxyurea- and CysNO-induced γ-globin expression. These data provide strong evidence for an NO-derived mechanism for HbF induction by hydroxyurea and suggest possibilities for therapies based on NO-releasing or -potentiating agents.
Valuable reputation gained by altruistic behavioral patterns
Authors: Claus Wedekind
Journal: Behavioral and Brain Sciences (2002)

On a proximate level, altruism may well be a temporally extended pattern of behavior that often seems to be maintained without extrinsic rewards (we may find it just valuable to be an altruistic person). However, recent theory and experiments have uncovered significant and often nonobvious extrinsic rewards for “altruistic” behavioral patterns. Ultimately, these patterns may mostly lead to a net benefit.
Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor–1 (Pref-1)
Authors: Kichoon Lee, Josep A. Villena, Yang Soo Moon, Kee-Hong Kim, Sunjoo Lee, Chulho Kang, Hei Sook Sul
Journal: Journal of Clinical Investigation (2003)

Preadipocyte factor-1 (Pref-1) is a transmembrane protein highly expressed in preadipocytes. Pref-1 expression is, however, completely abolished in adipocytes. The extracellular domain of Pref-1 undergoes two proteolytic cleavage events that generate 50 and 25 kDa soluble products. To understand the function of Pref-1, we generated transgenic mice that express the full ectodomain corresponding to the large cleavage product of Pref-1 fused to human immunoglobulin-γ constant region. Mice expressing the Pref-1/hFc transgene in adipose tissue, driven by the adipocyte fatty acid–binding protein (aP2, also known as aFABP) promoter, showed a substantial decrease in total fat pad weight. Moreover, adipose tissue from transgenic mice showed reduced expression of adipocyte markers and adipocyte-secreted factors, including leptin and adiponectin, whereas the preadipocyte marker Pref-1 was increased. Pref-1 transgenic mice with a substantial, but not complete, loss of adipose tissue exhibited hypertriglyceridemia, impaired glucose tolerance, and decreased insulin sensitivity. Mice expressing the Pref-1/hFc transgene exclusively in liver under the control of the albumin promoter also showed a decrease in adipose mass and adipocyte marker expression, suggesting an endocrine mode of action of Pref-1. These findings demonstrate the inhibition of adipogenesis by Pref-1 in vivo and the resulting impairment of adipocyte function that leads to the development of metabolic abnormalities.
Life Events, Subjective Stress, and Traffic Accidents
Authors: MELVIN L. SELZER, AMIRAM VINOKUR
Journal: American Journal of Psychiatry (1974)

In a departure from traditional personality-oriented traffic accident research, the authors assessed, through a self-administered questionnaire, the role of transitory life changes and subjective stress among 532 general and alcoholic male drivers. They found that these two factors were significantly correlated with traffic accidents but that personality and demographic variables were not. The need for additional research in this area is emphasized.
Congenital naevi treated with erbium:YAG laser (Derma K) resurfacing in neonates: clinical results and review of the literature
Authors: J.U. Ostertag, P.J.F. Quaedvlieg, F.E.M.J. Kerckhoffs, A.H.M. Vermeulen, M.J.O.E. Bertleff, A.W. Venema, S. van der Geer, G.A.M. Krekels
Journal: British Journal of Dermatology (2006)

Background Giant congenital melanocytic naevi (CMN) are often disfiguring, potentially malignant pigmented lesions present at birth. Their management is based on two main considerations: attempt to minimize the risk of malignancy and to obtain an acceptable cosmetic result. In the past various approaches have been used to treat these naevi. Objectives To describe clinical and histopathological results after treatment of CMN in neonates with erbium:YAG (Er:YAG) laser resurfacing. Methods Ten children with CMN were treated with Er:YAG laser resurfacing in the first weeks of life. Results Laser ablation was well tolerated by all children and immediate results were good. At a total follow-up ranging from 3 to 36 months we saw good results, with no or minimal repigmentation, in eight of 10 patients. Patients experienced minimal side-effects such as postoperative pain, bleeding and scar formation. Postoperative histopathology showed disappearance of heavily pigmented cells in the upper part of the dermis. Conclusions Er:YAG laser resurfacing is an effective method of ablating CMN, with minimal scarring and postoperative complications.
COMPARATIVE STUDIES UPON CANCER CELLS AND NORMAL CELLS
Authors: Robert A. Lambert
Journal: The Journal of Experimental Medicine (1913)

1. In primary cultures sarcoma cells exhibit a much greater activity than do normal connective tissue cells grown from the adult blood vessel; there is a shorter latent period, ameboid phenomena are more marked, and cell multiplication proceeds more rapidly. 2. In secondary cultures sarcoma cells are less active than in primary cultures; connective tissue cells, on the other hand, show a markedly accelerated growth. 3. Connective tissue cells are more easily propagated over long periods in vitro than are sarcoma cells; they multiply actively in cultures more than three months old. 4. The method of tissue cultivation is well adapted to the study of normal and pathological cell division; the nuclear changes are easily discernible in the living cell as division proceeds, and staining methods may be applied to verify observations upon the unstained structures. 5. Atypical mitoses of several kinds are found in cultures of sarcoma cells but are not seen in growths of connective tissue. 6. The time required for division in rat connective tissue cells kept at body temperature (38° C.) varies within relatively narrow limits (twenty to fifty minutes); sarcoma cells, on the contrary, exhibit marked variations and several hours may be required. 7. In studies upon living cells amitotic division has not been observed in either normal or tumor tissue. Evidences of nuclear budding, however, with the formation of cells containing several nuclei of irregular size have been noted.3 The development of a cell with two nuclei from a mononuclear cell by mitotic division of the nucleus without division of the cytoplasm has also been observed.
Uveitis in young adults with juvenile idiopathic arthritis: a clinical evaluation of 123 patients
Authors: K Kotaniemi
Journal: Annals of the Rheumatic Diseases (2005)

Objective: To examine the prevalence and characteristics of uveitis in young adults with juvenile idiopathic arthritis (JIA). Methods: The study population consisted of 123 JIA patients born between 1976 and 1980 whose arthritis had been diagnosed and treatment first started at the Rheumatism Foundation Hospital in 1976 to 1995. A clinical re-evaluation was carried out by an ophthalmologist and a paediatric rheumatologist 16 years later on average. Results: The mean age of the patients was 23.5 years, 72% were women, and 63% had oligoarthritis. During the course of the disease, diagnosis of uveitis had been made in 25 patients (20%). Arthritis in the 19 patients with asymptomatic uveitis was more often ongoing than in the 98 patients without uveitis (p = 0.032). Asymptomatic uveitis was persistent in eight of the 19 cases (42%), and arthritis was active in seven of these. Four of the six patients with attacks of symptomatic uveitis had parallel treatment for arthritis. In three of 19 patients with asymptomatic uveitis and in five of six with acute uveitis the eye inflammation had started after the age of 16. At the onset of arthritis the patients with asymptomatic uveitis were younger than those without uveitis (p = 0.002). Complications of uveitis developed in six patients but their sight remained good. Conclusions: Asymptomatic uveitis continued into adulthood in almost half the uveitis patients. Most also had ongoing arthritis. Acute uveitis was often associated with persistent arthritis.
Downregulation of Soluble Guanylyl Cyclase in Young and Aging Spontaneously Hypertensive Rats
Authors: Hartmut Ruetten, Ulrike Zabel, Wolfgang Linz, Harald H. H. W. Schmidt
Journal: Circulation Research (1999)

Endothelial dysfunction, as observed in hypertension and atherosclerosis, is associated with a reduction in the bioavailability of endothelium-derived nitric oxide (NO). We tested the hypothesis that alterations in the soluble guanylyl cyclase (sGC) pathway may also contribute to the pathogenesis of hypertension. Therefore, we investigated the expression and activity of sGC in young (6 weeks) and aging (17 months) spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto rats (WKY). Endothelium-independent relaxation of aortic rings in response to the sGC activator YC-1 was attenuated in SHR, and expression of both alpha(1) and beta(1) subunits of heterodimeric sGC and the basal contents of cGMP were reduced specifically in SHR aorta. Moreover, mRNA expression of the cGMP receptor and effector protein cGMP-dependent protein kinase type Ialpha (cGKIalpha) was also reduced. Interestingly, downregulation of both sGC and cGKIalpha expression was observed in young, ie, normotensive SHR, whereas impairment of the endothelium-independent relaxation was found only in aging SHR. Accordingly, similar cGMP levels were reached in response to YC-1 in young SHR and young WKY, suggesting a compensatory increased sensitivity or effectiveness of the sGC pathway in young SHR. In aging SHR, however, increased sensitivity to YC-1 no longer compensated for the impairment of endothelium-independent relaxation, suggesting that other mechanisms were involved. In fact, endothelium-independent relaxations were partially restored by superoxide dismutase, suggesting a pathophysiological role of superoxide production, particularly at later disease stages. Thus, tissue-specific downregulation of components of the sGC/cGMP pathway is an early event in the pathogenesis of hypertension.
Survival meta-analyses for &gt;1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1
Authors: M. Kolberg, M. Holand, T. H. Agesen, H. R. Brekke, K. Liestol, K. S. Hall, F. Mertens, P. Picci, S. Smeland, R. A. Lothe
Journal: Neuro-Oncology (2012)

There are conflicting reports as to whether malignant peripheral nerve sheath tumor (MPNST) patients with neurofibromatosis type 1 (NF1) have worse prognosis than non-NF1 MPNST patients. Large clinical studies to address this problem are lacking due to the rareness of MPNST. We have performed meta-analyses testing the effect of NF1 status on MPNST survival based on publications from the last 50 years, including only nonoverlapping patients reported from each institution. In addition, we analyzed survival characteristics for 179 MPNST patients from 3 European sarcoma centers. The meta-analyses including data from a total of 48 studies and >1800 patients revealed a significantly higher odds ratio for overall survival (OR(OS)) and disease-specific survival (OR(DSS)) in the non-NF1 group (OR(OS) = 1.75, 95% confidence interval [CI] = 1.28-2.39, and OR(DSS) = 1.68, 95% CI = 1.18-2.40). However, in studies published in the last decade, survival in the 2 patient groups has been converging, as especially the NF1 group has shown improved prognosis. For our own MPNST patients, NF1 status had no effect on overall or disease-specific survival. The compiled literature from 1963 to the present indicates a significantly worse outcome of MPNST in patients with NF1 syndrome compared with non-NF1 patients. However, survival for the NF1 patients has improved in the last decade, and the survival difference is diminishing. These observations support the hypothesis that MPNSTs arising in NF1 and non-NF1 patients are not different per se. Consequently, we suggest that the choice of treatment for MPNST should be independent of NF1 status.
Femoroacetabular impingement surgery: are we moving too fast and too far beyond the evidence?
Authors: Michael P Reiman, Kristian Thorborg
Journal: British Journal of Sports Medicine (2015)

Femoroacetabuler impingement (FAI) is becoming increasingly recognised as a potential pathological entity for individuals with hip pain. Surgery described to correct FAI has risen exponentially in the past 10 years with the use of hip arthroscopy. Unfortunately, the strength of evidence supporting both the examination and treatment of FAI does not appear to accommodate this exponential growth. In fact, the direction currently taken for FAI is similar to previously described paths of other orthopaedic and sports medicine pathologies (eg, shoulder impingement, knee meniscus tear) for which we have learned valuable lessons. The time has come for improved terminology, study design, and focus on delineation of successful treatment variables in the interest of those individuals with clinical indications of FAI so that we can appropriately address their needs.
Efficacy of mycophenolate mofetil in severe mucocutaneous lichen planus: a retrospective review of 10 patients
Authors: J.S. Wee, P.J. Shirlaw, S.J. Challacombe, J.F. Setterfield
Journal: British Journal of Dermatology (2012)

Ulcerative lichen planus is an uncommon and severe subtype of lichen planus primarily affecting the oral mucosal surfaces. It may be associated with significant morbidity and often requires immunosuppressive therapy to achieve disease control. There have been no previous reports in which objective outcome measures have been used to assess the efficacy of mycophenolate mofetil (MMF) in severe ulcerative lichen planus.To evaluate the clinical responses of patients with severe ulcerative oral lichen planus who were treated with MMF at a tertiary oral medicine/dermatology centre.This was a retrospective review of oral disease severity scores performed in 10 patients with recalcitrant ulcerative oral lichen planus (vulvovaginal-gingival, n = 8; penogingival, n = 1; oral, n = 1) before and after treatment with MMF therapy. The results were analysed using the Wilcoxon matched pairs signed-rank test.The mean duration of MMF treatment was 3·7 (SD ± 2·4) years with a mean follow-up of 4·2 (SD ± 2·7) years. The mean baseline oral disease severity scores (39·1 ± 11·9) improved by 40% after 12-15 months (24·3 ± 11·9, n = 8, P = 0·01) and by 43% after 21-24 months of MMF treatment (22·2 ± 10·4, n = 9, P = 0·01). Of the 10 patients, six achieved remission, one had well-controlled disease and three had partially controlled disease. Two patients who achieved remission successfully discontinued treatment. MMF was well tolerated in all patients.Our case series demonstrates the efficacy and favourable side-effect profile of MMF in the treatment of severe ulcerative lichen planus.
Hold the Patty, Not the Lettuce
Authors: Michael Miller
Journal: Circulation (2010)

early a century ago, Anichkov's keen experimental observations linking dietary cholesterol to accelerated atherosclerosis spawned an era of investigation assessing macronutrient intake in the development and progression of coronary heart disease (CHD). 1 To this end, epidemiological studies identified total fat, saturated fatty acid, and trans fatty acid (TFA) intake as positively correlated with CHD risk, 2 whereas intake of monounsaturated and polyunsaturated fatty acids was inversely correlated.
Activity of (-)-2'-deoxy-3'-oxacytidine (BCH-4556) against human tumor colony-forming units
Authors: L.L. Siu, G. Attardo, E. Izbicka, R. Lawrence, C. Cerna, L. Gomez, K. Davidson, C. Finkle, C. Marsolais, E.K. Rowinsky, D.D. Von Hoff
Journal: Annals of Oncology (1998)
Clinical Experience With the Addition of Pramlintide in Patients With Insulin-Requiring Type 2 Diabetes
Authors: Karen Elkind-Hirsch, William J. Butler, Madhu Bhushan, David Hirsch, Rajat Bhushan
Journal: Diabetes Care (2007)

Pramlintide, a synthetic amylin analog, was approved for type 2 diabetes as an adjunct treatment in patients who have failed to achieve desired glycemic control, despite optimal insulin therapy, with or without concomitant administration of oral antidiabetes agents (1). In clinical trials, pramlintide added to insulin treatment in patients with type 2 diabetes was shown to reduce postprandial glucose levels, improve glycemic control, and promote weight loss (2–8). We reviewed the medical records of our patients with type 2 diabetes who were on pramlintide in addition to insulin treatment to assess the efficacy of mealtime pramlintide on glycemic control and cardiometabolic risk factors in a single endocrine clinical practice setting.

We retrospectively studied laboratory and medical parameters of 92 insulin-treated adult patients with type 2 diabetes (54 female, 38 male, aged 24–80 years) recorded at baseline, 12 ± 4 weeks, and 24 ± 4 weeks after initiating pramlintide therapy. Medical and laboratory information were pulled from the main database of the Metabolic Center of Louisiana through a query that extracted information on all patients with type 2 diabetes treated with insulin who were unable to achieve glycemic control and who had completed at least 24 weeks of pramlintide treatment from June 2005 to November 2006. Patients with type 1 diabetes, patients with type …
Regional lung function and heterogeneity of specific gas volume in healthy and emphysematous subjects
Authors: Andrea Aliverti, Francesca Pennati, Caterina Salito, Jason C. Woods
Journal: European Respiratory Journal (2012)

The aim of our study was to study regional lung function by standard computed tomography (CT) and characterise regional variations of density and specific gas volume (SVg) between different lung volumes. We studied 10 healthy and 10 severely emphysematous subjects. Corresponding CT images taken at high and low lung volumes were registered by optical flow to obtain two-dimensional maps of pixel-by-pixel differences of density (ΔHU) and SVg (ΔSVg) at slice levels near the aortic arch, carina and top diaphragm. In healthy subjects, ΔHU was higher at all levels (p&lt;0.001) with higher variability expressed as interquartile range (p&lt;0.001), largely due to its differences between dorsal and ventral regions. In patients, median ΔSVg values were 3.2 times lower than healthy volunteers (p&lt;0.001), while heterogeneity of ΔSVg maps, expressed as quartile coefficient of variation, was 5.4 times higher (p&lt;0.001). In all patients, there were areas with negative values of ΔSVg. In conclusion, ΔSVg is uniform in healthy lungs and minimally influenced by gravity. The significant ΔSVg heterogeneity observed in emphysema allows identification of areas of alveolar destruction and gas trapping and suggests that ΔSVg maps provide useful information for evaluation and planning of emerging treatments that target trapped gas for removal.