tbuckley/cabot-search huggingface dataset:
Structural Brain Magnetic Resonance Imaging of Limbic and Thalamic Volumes in Pediatric Bipolar Disorder
Authors: Jean A. Frazier, Sufen Chiu, Janis L. Breeze, Nikos Makris, Nicholas Lange, David N. Kennedy, Martha R. Herbert, Eileen K. Bent, Vamsi K. Koneru, Megan E. Dieterich, Steven M. Hodge, Scott L. Rauch, P. Ellen Grant, Bruce M. Cohen, Larry J. Seidman, Verne S. Caviness, Joseph Biederman
Journal: American Journal of Psychiatry (2005)

Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities.Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled.The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen.These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.
PIK3CA Cooperates with Other Phosphatidylinositol 3′-Kinase Pathway Mutations to Effect Oncogenic Transformation
Authors: Katsutoshi Oda, Jennifer Okada, Luika Timmerman, Pablo Rodriguez-Viciana, David Stokoe, Keiko Shoji, Yuji Taketani, Hiroyuki Kuramoto, Zachary A. Knight, Kevan M. Shokat, Frank McCormick
Journal: Cancer Research (2008)

Abstract Mutations in genes functioning in different pathways frequently occur together in the same cancer, whereas mutations in the same pathway tend to be mutually exclusive. However, the majority of colon, breast, and endometrial cancers that possess mutations in PIK3CA, the catalytic subunit p110α of phosphatidylinositol 3′-kinase (PI3K), also possess mutations or alterations in genes upstream of PI3K such as Ras, ERBB2/ERBB3, or PTEN. PIK3CA mutations occur almost exclusively in invasive tumors, whereas upstream mutations occur as frequently in early-stage and late-stage tumors, suggesting that PIK3CA mutation is a late-stage event that may augment earlier activation of the PI3K pathway. Consistent with this, we find that levels of p-AKT (Ser473) induced by mutant Ras or knockdown of PTEN were dramatically increased by addition of mutant PIK3CA. Soft agar assays revealed that anchorage-independent growth induced by mutant Ras was greatly increased in the presence of mutant PIK3CA. In breast, colon, and endometrial cancers in which the PI3K pathway is activated by a combination of mutant PIK3CA and alterations in Ras, ERBB2/3, or PTEN, signaling to downstream elements such as Akt was mediated exclusively by the p110α isoform, rather than a combination of different PI3K isoforms. Our data therefore suggest that in tumors with co-occurring mutations in multiple components of the PI3K pathway, selective inhibition of the α isoform of p110 is an attractive therapeutic strategy, especially for late-stage tumors. [Cancer Res 2008;68(19):8127–36]
Symptomatic gastro-oesophageal reflux, abnormal oesophageal acid exposure, and mucosal acid sensitivity are three separate, though related, aspects of gastro-oesophageal reflux disease.
Authors: P J Howard, L Maher, A Pryde, R C Heading
Journal: Gut (1991)

The Bernstein test has been used as a test of oesophageal acid sensitivity for over 30 years but its clinical value has been challenged by the advent of ambulatory pH monitoring. Furthermore, the relation between mucosal acid sensitivity, symptomatic reflux, and abnormal oesophageal acid exposure time is unclear. This study examined the relation between these three parameters in patients referred for pH monitoring with unexplained chest pain or heartburn. Fifty consecutive patients were studied - nine with non-cardiac chest pain and 41 with a history of heartburn. Symptomatic reflux was defined as a greater than or equal to 50% temporal association between pain episodes and reflux events (pH less than 4) during pH monitoring. A positive acid perfusion test (in which the patient9s usual symptoms were evoked by acid, though not saline) had a 100% sensitivity, 73% specificity, and 81% accuracy for the detection of symptomatic reflux. All 10 patients with symptomatic reflux during pH monitoring had evidence of mucosal acid sensitivity. A negative acid perfusion test made symptomatic reflux unlikely. However, symptomatic reflux or a positive acid perfusion test, or both, were found in some patients with a normal oesophageal acid exposure time during pH monitoring. Mucosal acid sensitivity, abnormal oesophageal acid exposure time, and symptomatic reflux should be regarded as separate, though related aspects of reflux disease. The Bernstein test is simple, safe, and easily performed. A positive test helps to identify an oesophageal cause of symptoms, particularly in patients in whom other aspects of 9gastro-oesophageal reflux disease9 are absent, or who do not have symptoms during pH monitoring.
Successful treatment with fenofibrate, a peroxisome proliferator activated receptor ligand, for a patient with rheumatoid arthritis
Authors: H Okamoto
Journal: Annals of the Rheumatic Diseases (2004)

There is a well recognised association between rheumatoid arthritis (RA) and bronchiectasis.Walker observed a 10fold increased prevalence of bronchiectasis in RA. 1 The increased incidence of pulmonary disease in his study could not be explained by the greater susceptibility to infection by patients with RA because the symptoms of bronchiectasis preceded those of arthritis in the majority of the cases.Earlier reports found the prevalence of bronchiectasis in RA to be between 1 and 10%. 1 However, with the advent of high resolution computed tomography (HRCT) of the lung, later studies reported a prevalence of 25-30%. 2 3 This is important as HRCT is a more sensitive method of detecting bronchiectasis, and it is generally accepted that a chest radiograph may be normal in patients with bronchiectasis.Secondly, later studies investigated principally lifelong non-smoking patients with RA as opposed to the earlier studies, which investigated patients with RA irrespective of their smoking history.Cigarette smoking, particularly heavy cigarette smoking, is associated with the development of seropositive RA. 4 Likewise, it has been suggested that bronchiectasis may be a trigger for the development of RA. 5 To determine if these two potential risk factors for the development of RA are distinct we used HRCT to study patients with RA to determine if there are differences in the prevalence of smoking in patients with RA and bronchiectasis.
Cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) is more active than 5-fluorouracil, doxorubicin and methotrexate (FAMTX) in advanced gastric carcinoma
Authors: G. Cocconi, P. Carlini, A. Gamboni, S. Gasperoni, C. Rodinò, S. Zironi, G. Bisagni, S. Porrozzi, F. Cognetti, F. Di Costanzo, R. Canaletti, E.M. Ruggeri, R. Camisa, F. Pucci
Journal: Annals of Oncology (2003)
Polymorphisms of MTHFD, Plasma Homocysteine Levels, and Risk of Gastric Cancer in a High-Risk Chinese Population
Authors: Lina Wang, Qiao Ke, Wensen Chen, Jianming Wang, Yongfei Tan, Yan Zhou, Zhaolai Hua, Weiliang Ding, Juying Niu, Jing Shen, Zuofeng Zhang, Xinru Wang, Yaochu Xu, Hongbing Shen
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Accumulative evidence suggests that folate has a protective effect on gastric cancer. The methylenetetrahydrofolate dehydrogenase (MTHFD) plays an important role in folate and homocysteine metabolisms, and polymorphisms of MTHFD may result in disturbance of the folate-mediated homocysteine pathway. The aim of this study is to test the hypothesis that genetic variants of MTHFD and plasma homocysteine levels are associated with risk of gastric cancer and modulated by genotypes of methylenetetrahydrofolate reductase (MTHFR). Experimental Design: We genotyped G1958A and T401C in MTHFD and C677T in MTHFR and detected total plasma homocysteine (tHcy) levels in a case-control study of 589 gastric cancer cases and 635 cancer-free controls in a high-risk Chinese population. Results: The variant genotypes of MTHFD 1958AA and 401CC were associated with a significantly increased risk of gastric cancer [adjusted odds ratio (OR), 2.05; 95% confidence interval (95% CI), 1.34-3.13 for 1958AA; adjusted OR, 1.43; 95% CI, 1.14-1.80 for 401CC] compared with 1958GG/GA and 401TT/TC genotypes, respectively. Both of the effects were more evident in the subjects carrying MTHFR 677CT/TT genotypes. The average tHcy level was significantly higher in gastric cancer cases than in controls (P &amp;lt; 0.01), and the upper quartile of tHcy (&amp;gt;13.6 μmol/L) was associated with an 82% significantly increased risk of gastric cancer, compared with the lowest quartile of tHcy (≤8.0 μmol/L; adjusted OR, 1.82; 95% CI, 1.20-2.75). Conclusions: The strong associations between MTHFD variants and the plasma tHcy levels and gastric cancer risk suggest, for the first time, a possible gene-environment interaction between genetic variants of folate-metabolizing genes and high tHcy levels in gastric carcinogenesis.
Racial Differences in Predictors of Intensive End-of-Life Care in Patients With Advanced Cancer
Authors: Elizabeth Trice Loggers, Paul K. Maciejewski, Elizabeth Paulk, Susan DeSanto-Madeya, Matthew Nilsson, Kasisomayajula Viswanath, Alexi Anne Wright, Tracy A. Balboni, Jennifer Temel, Heather Stieglitz, Susan Block, Holly G. Prigerson
Journal: Journal of Clinical Oncology (2009)

Black patients are more likely than white patients to receive life-prolonging care near death. This study examined predictors of intensive end-of-life (EOL) care for black and white advanced cancer patients.Three hundred two self-reported black (n = 68) and white (n = 234) patients with stage IV cancer and caregivers participated in a US multisite, prospective, interview-based cohort study from September 2002 to August 2008. Participants were observed until death, a median of 116 days from baseline. Patient-reported baseline predictors included EOL care preference, physician trust, EOL discussion, completion of a Do Not Resuscitate (DNR) order, and religious coping. Caregiver postmortem interviews provided information regarding EOL care received. Intensive EOL care was defined as resuscitation and/or ventilation followed by death in an intensive care unit.Although black patients were three times more likely than white patients to receive intensive EOL care (adjusted odds ratio [aOR] = 3.04, P = .037), white patients with a preference for this care were approximately three times more likely to receive it (aOR = 13.20, P = .008) than black patients with the same preference (aOR = 4.46, P = .058). White patients who reported an EOL discussion or DNR order did not receive intensive EOL care; similar reports were not protective for black patients (aOR = 0.53, P = .460; and aOR = 0.65, P = .618, respectively).White patients with advanced cancer are more likely than black patients with advanced cancer to receive the EOL care they initially prefer. EOL discussions and DNR orders are not associated with care for black patients, highlighting a need to improve communication between black patients and their clinicians.
DNA Sequence Variants in Epithelium-Specific ETS-2 and ETS-3 Are Not Associated with Asthma
Authors: Rebecca M. Baron, Lyle J. Palmer, Kelan Tantisira, Stacey Gabriel, Larry A. Sonna, Louis Le, Arlene Hallock, Towia A. Libermann, Jeffrey M. Drazen, Scott T. Weiss, Eric S. Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Epithelium-specific ETS-2 and ETS-3 are transcription factors that have been proposed as asthma candidate genes. To investigate the association of sequence variants in these genes with asthma, we conducted a case–control association analysis in a sample of 311 white subjects with asthma and 177 white subjects without asthma. Common polymorphisms in these genes were detected by sequencing DNA from 32 cell lines obtained from Coriel (Camden, NJ). Seven noncoding or synonymous single-nucleotide polymorphisms were detected: three in epithelium-specific ETS-2 and four in epithelium-specific ETS-3. Subjects were genotyped at all loci by mass spectroscopy. To ensure the suitability of our control subjects, we also genotyped subjects at 49 unlinked polymorphisms evenly distributed throughout the autosomes and found no evidence of population stratification. Logistic regression adjusted for age and sex suggested a weak association of one epithelium-specific ETS-2 polymorphism with asthma diagnosis (odds ratio = 1.89, 95% confidence interval = 1.13–3.18, p = 0.02). Total serum immunoglobulin E and FEV1 predicted levels were not associated with any of the polymorphisms. Extended haplotyping indicated linkage disequilibrium in these genes; however, no association or epistatic interaction was found. This study suggests that epithelium-specific ETS-2 and ETS-3 genes are unlikely to contain polymorphic loci that have a major impact on asthma susceptibility in our population.
Increased gamma/delta-positive T-cells in blood and bronchoalveolar lavage of patients with sarcoidosis and hypersensitivity pneumonitis
Authors: M Raulf, V Liebers, C Steppert, X Baur
Journal: European Respiratory Journal (1994)

A small population of T-cells does not express the conventional T-cell receptor (TCR), characterized by the alpha and beta polypeptide chains (alpha/beta TCR) but two polypeptides termed gamma and delta (gamma/delta TCR). Changes in gamma/delta TCR expression may be relevant as the cause or consequence of several diseases. Our study was undertaken to determine and compare the distribution of T-cells expressing gamma/delta TCR in blood and bronchoalveolar lavage (BAL) of patients with sarcoidosis, hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF), and of healthy controls. In addition, the association between gamma/delta TCR of blood T-lymphocytes and accessory molecules was analysed. Using direct immunofluorescence with the anti-gamma/delta TCR and anti-CD3 monoclonal antibodies (MoAbs) followed by flow cytometric analysis, the blood of patients with pulmonary sarcoidosis, HP, IPF and of healthy controls was analysed. To reveal the association between gamma/delta TCR of blood T-lymphocytes and the accessory molecules, expression of CD4, CD8 and CD25 were determined. Calculating the percentage and the total number of CD3+ gamma/delta TCR cells in blood, the data indicated a significant increase of gamma/delta T-cells in individuals with pulmonary sarcoidosis and HP, compared to healthy controls and IPF patients. In sarcoidosis patients with elevated CD3+ gamma/delta TCR levels, significantly lower CD4/CD8 ratios were observed. In addition, our data demonstrate a correlation between the decrease of CD4+ cells in blood and the amplified appearance of gamma/delta TCR expression in sarcoidosis patients, but not in HP patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Mesothelial cells promote early ovarian cancer metastasis through fibronectin secretion
Authors: Hilary A. Kenny, Chun-Yi Chiang, Erin A. White, Elizabeth M. Schryver, Mohammed Habis, Iris L. Romero, Andras Ladanyi, Carla V. Penicka, Joshy George, Karl Matlin, Anthony Montag, Kristen Wroblewski, S. Diane Yamada, Andrew P. Mazar, David Bowtell, Ernst Lengyel
Journal: Journal of Clinical Investigation (2014)

Ovarian cancer (OvCa) metastasizes to organs in the abdominal cavity, such as the omentum, which are covered by a single layer of mesothelial cells. Mesothelial cells are generally thought to be “bystanders” to the metastatic process and simply displaced by OvCa cells to access the submesothelial extracellular matrix. Here, using organotypic 3D cultures, we found that primary human mesothelial cells secrete fibronectin in the presence of OvCa cells. Moreover, we evaluated the tumor stroma of 108 human omental metastases and determined that fibronectin was consistently overexpressed in these patients. Blocking fibronectin production in primary mesothelial cells in vitro or in murine models, either genetically (fibronectin 1 floxed mouse model) or via siRNA, decreased adhesion, invasion, proliferation, and metastasis of OvCa cells. Using a coculture model, we determined that OvCa cells secrete TGF-β1, which in turn activates a TGF-β receptor/RAC1/SMAD-dependent signaling pathway in the mesothelial cells that promotes a mesenchymal phenotype and transcriptional upregulation of fibronectin. Additionally, blocking α5 or β1 integrin function with antibodies reduced metastasis in an orthotopic preclinical model of OvCa metastasis. These findings indicate that cancer-associated mesothelial cells promote colonization during the initial steps of OvCa metastasis and suggest that mesothelial cells actively contribute to metastasis.
Desensitization for Dapsone Dermatitis
Authors: H. J. Smyly
Journal: BMJ (1963)

National Institute of Sciences of India on the history of sciences, including medicine, of ancient India.The following quotations from my paper with S. N. Pandeyal regarding the importance of theoretical and of practical training in medical education in ancient India will, I am sure, be of interest to your readers:1. " The student who obtains his know- ledge only from books is like an ass with a burden of sandalwood, for he knows the weight but not the value thereof."" 2. "He who is versed only in books, but not skilled in practice, gets alarmed and confused, like a coward in the battlefield when confronting active disease."3. "He who is skilled in practice but is audacious and ignorant of the theory cf scU'nce, does not receive approval of thK learned men and receives capital punishment from the king."4 4. " Both these groups of persons (items 2 and 3) are lacking in dexterity and inept in the discharge of their duties, for they know only half the science and are like birds with one wing only."51am.etc.,
Systemic lupus erythematosus--survival patterns. Experience with 609 patients
Authors: D. J. Wallace
Journal: JAMA (1981)

Six hundred nine private patients with systemic lupus erythematosus were followed up for a mean of ten years. Ninety percent were female; 79% were white. Three hundred sixty-nine received diagnosis before 1970, and 234 after. Three hundred seventy-nine did not have nephritis; 230 did. The overall ten-year survival was 79% (87% without nephritis, 65% with nephritis). Male patients did consistently worse than female patients. No overall white vs nonwhite difference was noted. The presence of nephrotic syndrome at the onset of nephritis was a poor prognostic sign, but its development later was not. Patients younger than 16 years without nephritis have an excellent prognosis. One hundred twenty-eight patients died (82 with nephritis, 46 without nephritis). The most common causes of death were renal disease and sepsis. Improved survival of this series may reflect closer follow-up, better nutritional status, and treatment at earlier stages of disease.
Ampicillin in Chronic Bronchitis
Authors: J. R. May
Journal: BMJ (1965)

Carcinogenesis of Isoniazid in Mice SIR,-Reports in the last few years that isoniazid in very large doses can produce pulmonary tumours in several strains of mice led to speculation that it might be carcino- genic for man.The need for investigation of the question has most recently been pointed out in these columns (12 June, p. 1508).
Is It Time for (Survivorship Care) Plan B?
Authors: Thomas J. Smith, Claire Snyder
Journal: Journal of Clinical Oncology (2011)

between docetaxel and gemcitabine in human gastric cancer cell lines. Clin Cancer Res 9:900-905, 2003 15. Hirth J, Watkins PB, Strawderman M, et al: The effect of an individual’s cytochrome CYP3A4 activity on docetaxel clearance. Clin Cancer Res 6:12551258, 2000 16. Hertz DL, Dees EC, Motsinger-Reif AA, et al: Breast cancer patients carrying the CYP2C8*3 variant are more likely to achieve clinical complete response from neoadjuvant paclitaxel treatment. Presented at the 33rd Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 8-12, 2010 (abstr PD07-10) 17. Berry DA: Adaptive clinical trials: The promise and the caution. J Clin Oncol 29:606-609, 2011 18. Woodcock J, Griffin JP, Behrman RE: Development of novel combination therapies. N Engl J Med 364:985-987, 2011
Influenza Virus Adaptation PB2-627K Modulates Nucleocapsid Inhibition by the Pathogen Sensor RIG-I
Authors: Michaela Weber, Hanna Sediri, Ulrike Felgenhauer, Ina Binzen, Sebastian Bänfer, Ralf Jacob, Linda Brunotte, Adolfo García-Sastre, Jonathan L. Schmid-Burgk, Tobias Schmidt, Veit Hornung, Georg Kochs, Martin Schwemmle, Hans-Dieter Klenk, Friedemann Weber
Journal: Cell Host & Microbe (2015)
Inhaled corticosteroids and lower lung function decline in young children with cystic fibrosis
Authors: K. De Boeck, F. Vermeulen, S. Wanyama, M. Thomas
Journal: European Respiratory Journal (2010)

A recent American registry analysis in cystic fibrosis (CF) children showed less lung function decline after starting inhaled corticosteroid (ICS) use. We therefore examined the influence of ICS treatment on lung function in Belgian CF patients. Data from patients ≥6 yrs of age were eligible, provided entries on lung function, height and ICS use were available in two consecutive years. Data after oral steroid use or transplant were excluded. 852 subjects contributed data with 2,976 data pairs analysed, 44.9% concerning years of ICS use. Yearly % predicted decline in forced expiratory volume in 1 s (FEV<sub>1</sub>) was 1.07% lower during ICS use (p = 0.001). Subgroup analysis for age revealed that the lower FEV<sub>1</sub> decline rate during ICS use was only statistically significant in children 6–12 yrs of age (2.56%; p = 0.0003). Baseline FEV<sub>1</sub> was lower by 5.89% (p&lt;0.0001) in ICS users for all age groups combined, but there was no difference in baseline lung function in the children 6–12 yrs of age. In 6–12-yr-old children with CF, baseline lung function was similar in ICS users and nonusers, but annualised FEV<sub>1</sub> decline was 2.56% pred lower in ICS users. Our data therefore support recent American findings.