tbuckley/cabot-search huggingface dataset:
Etiology of Pulmonary Artery Dilatation and Hilar Dance in Atrial Septal Defect
Authors: DEREK R. BOUGHNER, MARGOT R. ROACH
Journal: Circulation Research (1971)

Atrial septal defect is associated with increased diameter and pulsation of the pulmonary arteries. The high pulmonary flow rate produces turbulence and a murmur. Intraluminal pressure is normal and vessel wall elastic properties may be altered as in poststenotic dilatation. Pulmonary artery angiograms in 6 normal patients, 9 with pulmonary stenosis and 10 with atrial septal defect were recorded on film, projected and traced. Arterial diameters at maximum systole and diastole were measured and, with intraluminal pressures, 2 points on the elastic diagram were calculated. These points lay on the initial linear portion of the graph so that a line through them to zero wall tension gave the resting radius (R o ) Each radius value (R) was normalized by dividing by the corresponding R 0 . By plotting wall tension versus strain (R/R 0 ), a regression line was obtained for normals significantly different from that for poststenotic dilatation ( P &lt;0.01) and atrial septal defect ( P &lt;0.01). The slope of each line approximated vessel elastance at normal pressures: normals, 2.15 x 10 4 dyne/cm; poststenotic dilatation, 1.00 x 10 4 dyne/cm; and atrial septal defect, 0.89 x 10 4 dyne/cm. Increased pulmonary artery distensibility extends more peripherally in atrial septal defect, thus producing "hilar dance." A case of Marfan's syndrome showed similar changes.
Declines in Invasive Breast Cancer and Use of Postmenopausal Hormone Therapy in a Screening Mammography Population
Authors: K. Kerlikowske, D. L. Miglioretti, D. S. M. Buist, R. Walker, P. A. Carney
Journal: JNCI Journal of the National Cancer Institute (2007)

Whether a recent large decline in use of postmenopausal hormone therapy after the release of the Women's Health Initiative findings in July 2002 and/or a decline in screening mammography use is related to a recently reported decline in breast cancer incidence in the United States is controversial. We prospectively collected data from four screening mammography registries from January 1997 through December 2003 for 603411 screening mammography examinations performed on women aged 50–69 years. Of these women, 3238 were diagnosed with breast cancer within 12 months of a screening examination. We calculated quarterly rates of self-reported current postmenopausal hormone therapy use and of invasive breast cancer, ductal carcinoma in situ (DCIS), and estrogen receptor (ER)–positive invasive breast cancer adjusted for age, registry, and time between screening examinations. All statistical tests were two-sided. Between 2000 and 2002 and between 2002 and 2003, annual rates of postmenopausal hormone therapy use declined by 7% and 34%, respectively ( Ptrend <.001 for both). Between 2000 and 2003, annual rates of invasive cancer declined by 5% ( Ptrend =.003). Between 2001 and 2003, annual rates of ER-positive invasive breast cancer declined by 13% ( P trend =.002). Rates of DCIS were stable during the study period. Our finding of a statistically significant decline in the rate of ER-positive invasive breast cancer in a screening mammography population after the start of a concomitant substantial decline in postmenopausal hormone therapy use suggests that a decline in screening mammography rates is unlikely to account for the recent decline in US breast cancer incidence.
Screening-Preventable Cervical Cancer Risks: Evidence From a Nationwide Audit in Sweden
Authors: B. Andrae, L. Kemetli, P. Sparen, L. Silfverdal, B. Strander, W. Ryd, J. Dillner, S. Tornberg
Journal: JNCI Journal of the National Cancer Institute (2008)

The effectiveness of cervical cancer screening programs differs widely in different populations. The reasons for these differences are unclear. Routine and comprehensive audits have been proposed as an ethically required component of screening. We performed a nationwide audit of the effectiveness of the Swedish cervical cancer screening program. We identified all invasive cervical cancer cases that were diagnosed in Sweden from January 1, 1999, through December 31, 2001, and had been reported to the Swedish Cancer Registry (n = 1230 cases). We verified the diagnoses by histopathologic rereview and matched each case subject to five (population-based) age-matched control subjects who were identified from the National Population Register. The Pap smear screening histories for case and control subjects were reviewed for a 6-year period using the National Cervical Cancer Screening Register, which contains data on essentially all relevant cytological and histological diagnoses in Sweden. Odds ratios (ORs), and their 95% confidence intervals (CIs), of cervical cancer according to screening history were calculated in conditional logistic regression models. All statistical tests were two-sided. Women who had not had a Pap smear within the recommended screening interval had higher risk of cervical cancer than women who had been screened (OR = 2.52, 95% CI = 2.19 to 2.91). This risk was similarly increased for all age groups ( Phomogeneity = .96). The risk for nonsquamous cell cervical cancers (OR = 1.59, 95% CI = 1.20 to 2.11) was also increased. Women who had not had a Pap smear within the recommended screening interval had a particularly high risk of advanced cancers (OR = 4.82, 95% CI = 3.61 to 6.44). Among women who had been screened within the recommended interval, those with abnormal Pap smears had a higher risk of cervical cancer than those with normal smears (OR = 7.55, 95% CI = 5.88 to 9.69) and constituted 11.5% of all women with cervical cancer. Nonadherence to screening intervals was the major reason for cervical cancer morbidity. The screening program was equally effective for women of all ages and was also effective against nonsquamous cancers.
Synthetic Lethality through Combined Notch–Epidermal Growth Factor Receptor Pathway Inhibition in Basal-Like Breast Cancer
Authors: Yiyu Dong, Aimin Li, Jianbo Wang, Jason D. Weber, Loren S. Michel
Journal: Cancer Research (2010)

Basal-like breast cancers (BLBC) are highly aggressive, yet selective therapies targeting the specific oncoproteins driving these tumors have not been developed. These cancers frequently express epidermal growth factor receptor (EGFR), with resistance to its inhibition being well documented, albeit poorly understood. Notch pathway activation is also common in this breast cancer subtype and can be suppressed by gamma-secretase inhibitors, which effectively block receptor cleavage and activation. Herein, we show that although inhibition of either EGFR or Notch signaling alone is insufficient to suppress basal-like breast tumor cell survival and proliferation, simultaneous inhibition uncovers a synthetic lethal relationship between these two oncogenic pathways. This lethality is due in part to significant decreases in AKT activation caused by combined EGFR and Notch inhibition. Expression of the activated form of Notch1 restores AKT activity and enables cells to overcome cell death after dual-pathway blockade. Combined pathway inhibition is also dramatically more effective at suppressing tumor growth in mice than blocking EGFR or Notch signaling alone. Thus, we show that Notch pathway activation contributes to resistance to EGFR inhibition, and provide a novel treatment strategy for BLBCs.
Role of thyroxine in chronic urticaria and angio-oedema
Authors: C. Cusack, D. J. O Gorman
Journal: Journal of the Royal Society of Medicine (2004)

Obesity in Chinese children I do not wish to add fuel to the fire by entering into a discussion on food advertising versus physical inactivity as the culprit for childhood obesity that was prompted by Dr Ashton's editorial (February 2004 JRSM 1 ).I always tell my overweight or obese patients that body fat does not grow on the tree; it has to come from an external source, either overeating or underexertion.The best example comes from China.China used to be known for her slender people; I never saw a fat person in China until very recently. 2Now China is fighting obesity, especially childhood obesity, just like the rest of the world.According to the latest statistics from China, the proportion of obesity among children under the age of 15 increased from 15% in 1982 to 27% today. 3Among the predisposing factors for increasing prevalence of childhood obesity in China, fast food and physical inactivity are the two most important.Because of the efficient advertisements of such fast food giants in the United States as McDonald's and Kentucky Fried Chicken, Chinese children are devouring the American fast food faster than ever. 2,4All of the children in China recognize the image of Ronald McDonald, even though they might not be able to read English. 4hat physical inactivity is the other important risk factor for obesity in Chinese children is illustrated by three observations.First, the effect of television on childhood obesity in China has been documented: each hourly increment of television viewing is associated with a 1-2% increase in the prevalence of obesity in urban China. 5econd, childhood obesity is more prevalent in urban areas than in rural areas, not only because children in rural China are physically more active 6 but also because urban boys consume more fat than rural boys-23-30% versus 16-20%. 7Third, urban children in China are engaged in more homework because they are under pressure to achieve scholastically, whereas rural Chinese children are engaged more in field work because of economic necessity.
Malonyl-CoA, a Key Signaling Molecule in Mammalian Cells
Authors: David Saggerson
Journal: Annual Review of Nutrition (2008)

Malonyl-CoA can be formed within the mitochondria, peroxisomes, and cytosol of mammalian cells. Besides being an intermediate in the pathways of de novo fatty acid biosynthesis and fatty acid elongation, malonyl-CoA has an important signaling function through its allosteric inhibition of carnitine palmitoyltransferase 1, the enzyme that normally exerts flux control over mitochondrial beta-oxidation. Malonyl-CoA is rapidly turned over in mammalian cells, and the activities of acetyl-CoA carboxylase and malonyl-CoA decarboxylase are important determinants of its cytosolic concentration. It is now recognized that malonyl-CoA participates in a diverse range of physiological or pathological responses and systems. These include the ketogenic response of the liver to fasting and diabetes, carbohydrate versus fat fuel selection in muscle tissues, metabolic changes in muscle during contracture, alterations in fatty acid metabolism during cardiac ischemia and postischemic reperfusion, stimulation of B cell insulin secretion by glucose, and the hypothalamic control of appetite.
Glycated Hemoglobin Predicts All-Cause, Cardiovascular, and Cancer Mortality in People Without a History of Diabetes Undergoing Coronary Angiography
Authors: Guenther Silbernagel, Tanja B. Grammer, Bernhard R. Winkelmann, Bernhard O. Boehm, Winfried März
Journal: Diabetes Care (2011)

Glycated hemoglobin has been suggested to be superior to fasting glucose for the prediction of vascular disease and death from any cause. The aim of the present work was to analyze and compare the predictive value of glycated hemoglobin and fasting glucose on all-cause and cause-specific mortality in subjects who underwent coronary angiography.We studied 2,686 participants of the Ludwigshafen Risk and Cardiovascular health study without a history of diabetes. The majority of this cohort had coronary artery disease. Glycated hemoglobin was measured at the baseline examination. The mean (± SD) duration of the follow-up for all-cause, cardiovascular, and cancer mortality was 7.54 ± 2.1 years.A total of 508 deaths occurred during the follow-up. Of those, 299 were accounted for by cardiovascular diseases and 79 by cancer. Baseline glycated hemoglobin was predictive of all-cause, cardiovascular, and cancer mortality. The multivariable-adjusted hazard ratios (HR) (95% CI) for glycated hemoglobin values of <5.0, 5.0-5.4, 5.5-5.9, 6.0-6.4, 6.5-7.4, and ≥7.5% for all-cause mortality were 1.36 (0.85-2.18), 1.00 (0.76-1.32), 1.00 (reference), 1.11 (0.88-1.41), 1.39 (1.07-1.82), and 2.15 (1.32-3.53), respectively. Similar J-shaped relationships were found between glycated hemoglobin and cardiovascular and cancer mortality. The associations of glycated hemoglobin with all-cause and cardiovascular mortality remained significant after inclusion of fasting glucose as a covariate. However, fasting glucose was not significantly related to mortality when adjusting for glycated hemoglobin.Glycated hemoglobin significantly and independently of fasting glucose predicts all-cause and cardiovascular mortality in whites at intermediate to high cardiovascular risk.
CYFIP1 Coordinates mRNA Translation and Cytoskeleton Remodeling to Ensure Proper Dendritic Spine Formation
Authors: Silvia De Rubeis, Emanuela Pasciuto, Ka Wan Li, Esperanza Fernández, Daniele Di Marino, Andrea Buzzi, Linnaea E. Ostroff, Eric Klann, Fried J.T. Zwartkruis, Noboru H. Komiyama, Seth G.N. Grant, Christel Poujol, Daniel Choquet, Tilmann Achsel, Danielle Posthuma, August B. Smit, Claudia Bagni
Journal: Neuron (2013)

The CYFIP1/SRA1 gene is located in a chromosomal region linked to various neurological disorders, including intellectual disability, autism, and schizophrenia. CYFIP1 plays a dual role in two apparently unrelated processes, inhibiting local protein synthesis and favoring actin remodeling. Here, we show that brain-derived neurotrophic factor (BDNF)-driven synaptic signaling releases CYFIP1 from the translational inhibitory complex, triggering translation of target mRNAs and shifting CYFIP1 into the WAVE regulatory complex. Active Rac1 alters the CYFIP1 conformation, as demonstrated by intramolecular FRET, and is key in changing the equilibrium of the two complexes. CYFIP1 thus orchestrates the two molecular cascades, protein translation and actin polymerization, each of which is necessary for correct spine morphology in neurons. The CYFIP1 interactome reveals many interactors associated with brain disorders, opening new perspectives to define regulatory pathways shared by neurological disabilities characterized by spine dysmorphogenesis.
Two cheers for GINA?
Authors: Amy L McGuire, Mary Majumder
Journal: Genome Medicine (2009)

The Genetic Information Nondiscrimination Act of 2008 (GINA) was recently enacted in the United States. Its supporters have applauded the passage of GINA, and they hope that it will alleviate public fear about genetic discrimination and facilitate genetic testing and participation in genetic research. Critics worry that GINA does not provide adequate protection because it fails to address discrimination on the basis of non-genetic health-related information, and it only regulates the use of genetic information in health insurance and employment. Despite these limitations, GINA represents a major step forward in US policy. Additional research is needed to assess the impact of GINA on industry practice and public opinion. In the mean time, education about GINA and its limitations can help individuals make more informed decisions about genetic testing and participation in genetic research.
Blinded by the Light: Molecular Imaging in Pancreatic Adenocarcinoma
Authors: Eric Collisson, Margaret Tempero
Journal: Clinical Cancer Research (2010)

The early detection and optimal perisurgical management of pancreatic adenocarcinoma are paramount goals in our quest to increase cure rates in this lethal malignancy. Molecular imaging techniques may be the conduit through which new genomic and proteomic discoveries about this disease are brought to the clinic.
Treatment of (NZB x NZW)F1 disease with anti-I-A monoclonal antibodies.
Authors: N E Adelman, D L Watling, H O McDevitt
Journal: The Journal of Experimental Medicine (1983)

(NZB x NZW)F1 mice spontaneously develop an autoimmune syndrome characterized by a fatal immune complex glomerulonephritis. Administration of monoclonal antibodies specific for an I region gene product (I-Az) of the H-2 haplotype associated with susceptibility to glomerulonephritis in these animals produced a remission in female mice with established renal disease. The results demonstrated that anti-I-A therapy stabilized the level of proteinuria and increased the 1-yr survival rate from 10% to greater than 90% in treated animals relative to control mice. These findings may ultimately have therapeutic potential for the treatment of systemic lupus erythematosus.
A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse
Authors: Patrick M. Nolan, Jo Peters, Mark Strivens, Derek Rogers, Jim Hagan, Nigel Spurr, Ian C. Gray, Lucie Vizor, Debra Brooker, Elaine Whitehill, Rebecca Washbourne, Tertius Hough, Simon Greenaway, Mazda Hewitt, Xinhong Liu, Stefan McCormack, Karen Pickford, Rachael Selley, Christine Wells, Zuzanna Tymowska-Lalanne, Phil Roby, Peter Glenister, Claire Thornton, Caroline Thaung, Julie-Anne Stevenson, Ruth Arkell, Philomena Mburu, Rachel Hardisty, Amy Kiernan, Alexandra Erven, Karen P. Steel, Stephanie Voegeling, Jean-Louis Guenet, Carole Nickols, Ramin Sadri, Mahmood Naase, Adrian Isaacs, Kay Davies, Mick Browne, Elizabeth M.C. Fisher, Jo Martin, Sohaila Rastan, Steve D.M. Brown, Jackie Hunter
Journal: Nature Genetics (2000)
Body and Liver Fat Mass Rather Than Muscle Mitochondrial Function Determine Glucose Metabolism in Women With a History of Gestational Diabetes Mellitus
Authors: Thomas Prikoszovich, Christine Winzer, Albrecht Ingo Schmid, Julia Szendroedi, Marek Chmelik, Giovanni Pacini, Martin Krššák, Ewald Moser, Tohru Funahashi, Werner Waldhäusl, Alexandra Kautzky-Willer, Michael Roden
Journal: Diabetes Care (2010)

Ectopic lipid storage in muscle (intramyocellular lipids [IMCL]) and liver (hepatocellular lipids [HCL]) coexists with impaired myocellular flux through ATP synthase (fATPase) in certain cohorts with increased risk of type 2 diabetes. Because women with a history of gestational diabetes mellitus (pGDM) have elevated ectopic lipids and diabetes risk, we tested whether deteriorated energy metabolism contributes to these abnormalities.A total of 23 glucose-tolerant nonobese pGDM and eight women with normal glucose metabolism during pregnancy with similar age, body mass, and physical activity underwent oral glucose tolerance tests (OGTT) and intravenous glucose tolerance tests at 4-5 years after delivery. OGTT values <463 mL ⋅ min(-1) ⋅ m(-2) were considered to indicate insulin resistance. pGDM were further stratified into insulin-resistant (pGDM-IR) and insulin-sensitive (pGDM-IS) groups. IMCL, HCL, and fATPase were measured with (1)H/(31)P magnetic resonance spectroscopy.pGDM had 36% higher fat mass and 12% lower insulin sensitivity. Log-transformed fATPase was lower in pGDM (10.6 ± 3.8 µmol ⋅ mL muscle(-1) ⋅ min(-1) vs. 12.1 ± 1.4 µmol ⋅ mL muscle(-1) ⋅ min(-1), P < 0.03) and related to plasma adiponectin after adjustment for body fat (r = 0.44, P < 0.04). IMCL were 61% and 69% higher in pGDM-IR (P < 0.05 vs. pGDM-IS) and insulin resistant women (P < 0.003 vs. insulin sensitive), respectively. HCL were doubled (P < 0.05) in pGDM and insulin resistant women, and correlated positively with body fat mass (r = 0.50, P < 0.01) and inversely with insulin sensitivity (r = -0.46, P < 0.05).Glucose-tolerant pGDM show increased liver fat but only slightly lower muscular insulin sensitivity and ATP synthesis. This suggests that alteration of hepatic lipid storage represents an early and predominant abnormality in this cohort.
Relation between Heberden's nodes and distal interphalangeal joint osteophytes and their role as markers of generalised disease
Authors: F. M Cicuttini, J. Baker, D. J Hart, T. D Spector
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> Heberden's nodes are often used as a marker for osteoarthritis (OA). This study examined how often Heberden's nodes and radiological distal interphalangeal (DIP) osteophytes coexist in the same digit and the sensitivity, specificity, and positive predicative value of each for OA at different sites or generalised disease. <h3>METHODS</h3> This was a population-based study of 660 middle aged women taking part in a twin study of OA. Distal interphalangeal osteophytes were defined radiologically and graded on a four point scale (0–3) using a published atlas of individual features. Heberden's nodes were defined by standardised clinical examination. OA in other joints (knees, proximal interphalangeal (PIP) joints and carpometacarpal (CMC) joints) was defined radiologically using a published atlas. <h3>RESULTS</h3> Poor agreement was observed between a Heberden's node (HN) and a radiological distal interphalangeal osteophyte in the same finger of the same hand (κ statistic (95% CI) = 0.36 (0.33, 0.39)). Although HN and radiological DIP osteophytes had similar sensitivity, the specificity and positive predicative value of DIP osteophytes was considerably higher for detecting knee, CMC, PIP OA, and OA in more than two groups of joints (knee, CMC, and DIP joints). <h3>CONCLUSION</h3> HN are not synonymous with DIP osteophytes. Radiological DIP osteophytes are a better marker of knee and multiple joint OA than HN. HN may still be an imperfect surrogate for hand OA when radiology is impractical, but are not an accurate marker of generalised disease.
Cell interactions in the suppression of in vitro antibody responses.
Authors: C E Calkins, S Orbach-Arbouys, O Stutman, R K Gershon
Journal: The Journal of Experimental Medicine (1976)

Normal T and immune B lymphocytes interact in a fashion that leads to suppression of the immune response. Normal spleen cells added to cultures of primed spleen cells specifically suppressed both the IgM and IgG secondary antibody response of the primed cells to less than 30% of the response of the immune cells cultured alone. Cell crowding as a possible in vitro artifact was ruled out. The suppression was specific for the priming antigen, even when the specific and nonspecific antigens were included in the same cultures. Suppression required both normal T and immune B cells to be present in culture. We suggest that the immune population produces a signal that can induce normal T cells to become specific suppressor cells. This form of interaction may represent an important regulatory (homeostatic) mechanism in the immune system.