tbuckley/cabot-search huggingface dataset:
Interleukin 10 inhibits growth and granulocyte/macrophage colony-stimulating factor production in chronic myelomonocytic leukemia cells.
Authors: K Geissler, L Ohler, M Födinger, I Virgolini, M Leimer, E Kabrna, M Kollars, S Skoupy, B Bohle, M Rogy, K Lechner
Journal: The Journal of Experimental Medicine (1996)

Autonomous release of hematopoietic growth factors may play a crucial role in the pathogenesis of certain hematological malignancies. Because of its cytokine synthesis-inhibiting action, interleukin 10 (IL-10) could be a potentially useful molecule to affect leukemic cell growth in such disorders. Chronic myelomonocytic leukemia (CMML) cells spontaneously form myeloid colonies (colony-forming units-granulocyte/macrophage) in methylcellulose, suggesting an autocrine growth factor-mediated mechanism. We studied the effect of recombinant human IL-10 (rhIL-10) on the in vitro growth of mononuclear cells obtained from peripheral blood or bone marrow of patients with CMML. IL-10 specifically binding to leukemic cells had a profound and dose-dependent inhibitory effect on autonomous in vitro growth of CMML cells. IL-10 significantly inhibited the spontaneous growth of myeloid colonies in methylcellulose in 10/11 patients, and autonomous CMML cell growth in suspension in 5/5 patients tested. Spontaneous colony growth from CMML cells was also markedly reduced by addition of antigranulocyte/macrophage colony-stimulating factor (GM-CSF) antibodies, but not by addition of antibodies against G-CSF, IL-3, or IL-6, IL-10-induced suppression of CMML cell growth was reversed by the addition of exogenous GM-CSF and correlated with a substantial decrease in GM-CSF production by leukemic cells, both at the mRNA and protein levels. Our data indicate that IL-10 profoundly inhibits the autonomous growth of CMML cells in vitro most likely through suppression of endogenous GM-CSF release. This observation suggests therapeutic evaluation of rhIL-10 in patients with CMML.
Benign familial hypermobility syndrome and Trendelenburg sign in a painting “The Three Graces” by Peter Paul Rubens (1577–1640)
Authors: J DEQUEKER
Journal: Annals of the Rheumatic Diseases (2001)

Clinical features suggestive of hypermobility syndrome and a positive Trendelenburg sign are described in a painting "The Three Graces" (1638-1640) by Peter Paul Rubens, Prado, Madrid. The most obvious findings are scoliosis, positive Trendelenburg sign, and hyperextension of the metacarpal joints, hyperlordosis, and flat feet. The sitters, presumably Hélène Fourment (second wife of Rubens) and her sisters, support the hereditary familial aspect of hypermobility. Manifest hypermobility of the hand has also been found in two other ancient paintings: "Saint Cyriaque" in the Heller Retable by Mathias Grünewald (1450-1528), Frankfurt, and "The wounded man" by Gaspare Traversi, Venice (1732-1769). The finding of signs of hypermobility in ancient paintings shows that artists who are keen observers of nature could describe, or at least record, this condition long before doctors did. The art of the past can be a useful tool in the field of paleopathology.
The Effect of Exercise and Nutrition on Intramuscular Fat Metabolism and Insulin Sensitivity
Authors: Christopher S. Shaw, Juliette Clark, Anton J.M. Wagenmakers
Journal: Annual Review of Nutrition (2010)

Intramuscular triacylglycerol (IMTG) is both a dynamic fat-storage depot that can expand during periods of elevated lipid availability and a fatty acid source that can be utilized during periods of increased energy expenditure in active individuals. Although many studies have investigated the lifestyle determinants of IMTG content, the results are far from consistent, and studies attempting to unravel the mechanisms behind IMTG metabolism are in their infancy. The limited evidence available suggests that the enzymes responsible for skeletal muscle lipolysis and IMTG synthesis play an important role in determining the fate of fatty acids and therefore the concentration of lipid metabolites and insulin sensitivity of skeletal muscle. This review provides a summary of current knowledge on the effects of acute and chronic exercise as well as energy intake and macronutrient composition of the diet upon the metabolism of IMTG and the implications for metabolic health.
TRAIL: not just for tumors anymore?
Authors: Chris A. Benedict, Carl F. Ware
Journal: The Journal of Experimental Medicine (2012)

Since the discovery of TNF-related apoptosis-inducing ligand (TRAIL) and its network of receptors, the majority of attention has focused on the clinical potential of manipulating this pathway in cancer therapy. However, the widespread expression of TRAIL under inflammatory conditions and the ability to induce both apoptotic and prosurvival signaling pathways has suggested that TRAIL plays broader roles in regulating immune processes. Two new studies now show that expression of TRAIL by neutrophils in the lung facilitates defenses against bacterial pathogens, whereas expression of TRAIL by cells within arterioles exacerbates vascular disease. These differentiating results highlight that the context of TRAIL signaling can determine whether the outcome is beneficial or pathogenic for the host.
MENTAL DEFECT IN EPILEPSY AND THE INFLUENCE OF HEREDITY
Authors: WILLIAM G. LENNOX
Journal: American Journal of Psychiatry (1942)

Reports concerning approximately 1900 extramural patients have been analyzed with respect to the present mental state of these patients and the determining influence of heredity on their mentality. Among these patients 64 per cent were mentally normal and only 14 per cent definitely deteriorated, in spite of the fact that the average patient had experienced 2000 seizures during a period of 8 years. The relatives of epileptic patients are more affected by mental disorders of various sorts than the normal population. Patients with essential epilepsy have more relatives with both epilepsy and neuropsychiatric disorders than patients with symptomatic epilepsy. The difference is more pronounced for fathers than for other members of the patient's family. Patients who were mentally abnormal at birth had approximately twice as many relatives with epilepsy and with psychosis as patients who were normal at birth. Patients whose mentality was normal at birth but is now abnormal have only a few more epileptic relatives than patients whose mentality has been persistently normal. Whatever the mentality of the patient at birth, the earlier in life seizures appeared, the greater was the number of relatives with epilepsy. These data indicate that heredity plays a rôle in the impaired mentality of certain patients subject to seizures. This rôle relatively small if patients were mentally normal before the seizures began. Other causes of mental impairment will be discussed in subsequent communications.
Elevated C-Reactive Protein Associates With Early-Stage Carotid Atherosclerosis in Young Subjects With Type 1 Diabetes
Authors: Rieko Hayaishi-Okano, Yoshimitsu Yamasaki, Naoto Katakami, Kentaro Ohtoshi, Shin-Ichi Gorogawa, Akio Kuroda, Munehide Matsuhisa, Keisuke Kosugi, Norikiyo Nishikawa, Yoshitaka Kajimoto, Masatsugu Hori
Journal: Diabetes Care (2002)

To evaluate whether low-grade inflammation contributes to early-stage advanced carotid atherosclerosis in young subjects with type 1 diabetes.The mean and maximum (max) intima-media thicknesses (IMT) of the carotid artery were assessed using ultrasound B-mode imaging in 55 patients with type 1 diabetes (22 men and 33 women, aged 22.1 +/- 3.6 years (+/- SD), duration of diabetes 14.2 +/- 5.7 years) and 75 age-matched healthy nondiabetic subjects (28 men and 47 women). High-sensitive C-reactive protein (hs-CRP) levels were measured with a latex-enhanced immunonephelometer.The patients with type 1 diabetes had significantly higher hs-CRP levels (median 0.35, range 0.05-1.47 mg/l vs. median 0.14, range 0.05-1.44 mg/l; P = 0.001) as well as significantly higher mean IMT and max IMT than the nondiabetic subjects (mean IMT 0.76 +/- 0.09 vs. 0.72 +/- 0.04 mm, P = 0.003; max IMT 0.84 +/- 0.11 vs. 0.77 +/- 0.06 mm, P < 0.0001). Hs-CRP levels were significantly correlated with the mean and max IMT of patients with type 1 diabetes and with the max IMT of nondiabetic patients. Multivariate regression analyses for both diabetic and nondiabetic subjects as a single group showed that hs-CRP levels are independently correlated with the mean IMT and max IMT levels (P = 0.002 and P = 0.023, respectively) as well as with diastolic blood pressure, sex, and duration of diabetes.Our data indicate that hs-CRP levels are elevated in young patients with type 1 diabetes, possibly corresponding with early-stage advanced carotid atherosclerosis.
Nitric Oxide Synthase Variants and Disease-Free Survival among Treated and Untreated Breast Cancer Patients in a Southwest Oncology Group Clinical Trial
Authors: Ji-Yeob Choi, William E. Barlow, Kathy S. Albain, Chi-Chen Hong, Javier G. Blanco, Robert B. Livingston, Warren Davis, James M. Rae, I-Tien Yeh, Laura F. Hutchins, Peter M. Ravdin, Silvana Martino, Alan P. Lyss, C. Kent Osborne, Martin D. Abeloff, Daniel F. Hayes, Christine B. Ambrosone
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Numerous chemotherapeutic agents are cytotoxic through generation of reactive species, and variability in genes related to oxidative stress may influence disease-free survival (DFS). We examined relationships between DFS and variants in NOS3, as well as NQO1, NQO2, and CBR3, among treated and untreated breast cancer patients in a Southwest Oncology Group clinical trial (S8897). Experimental Design: In the parent trial, women were assigned according to prognostic features; the high-risk group was randomized to cyclophosphamide, i.v. methotrexate, and 5-fluorouracil or to cyclophosphamide, i.v. doxorubicin, and 5-fluorouracil ± tamoxifen, and the low-risk group did not receive adjuvant therapy. We extracted DNA from normal lymph node tissue and examined functional polymorphisms in NOS3, NQO1, NQO2, and CBR3, in relation to DFS, using Cox proportional hazard model. Results: There were significant interactions between DFS, adjuvant therapy, and NOS3 Glu298Asp and −786 polymorphisms, alone and in combination (P for interaction = 0.008). When NOS3 genotypes were combined, women with genotypes encoding for lower nitric oxide who received chemotherapy had a &amp;gt;2-fold increase in hazard of progression (hazard ratio, 2.32; 95% confidence interval, 1.26-4.25), whereas there was reduced risk for those who did not receive adjuvant therapy (hazard ratio, 0.42; 95% confidence interval, 0.19-0.95). There were no associations between the other genotypes and DFS in either group. Conclusion: Variants encoding lower activity of NOS3 may affect outcomes in breast cancer patients, with the direction of risk differing depending on chemotherapy status. These results may mirror the known dual functions of nitric oxide and nitric oxide synthase, depending on oxidative environment. (Clin Cancer Res 2009;15(16):5258–66) (Clin Cancer Res 2009;15(16):5258–)
Rye grass is associated with fewer non-contact anterior cruciate ligament injuries than bermuda grass
Authors: J W Orchard, I Chivers, D Aldous, K Bennell, H Seward
Journal: British Journal of Sports Medicine (2005)

To assess the contribution of ground variables including grass type to the rate of anterior cruciate ligament (ACL) injury in the Australian Football League (AFL), specifically which factors are primarily responsible for previously observed warm season and early season biases for ACL injuries.Grass types used at the major AFL venues from 1992 to 2004 were established by consultation with ground managers, and ground hardness and other weather variables were measured prospectively.There were 115 ACL injuries occurring in matches during the survey time period, 88 with a non-contact mechanism. In multivariate analysis, use of bermuda (couch) grass as opposed to rye grass, higher grade of match, and earlier stage of the season were independent risk factors for non-contact ACL injury. Ground hardness readings did not show a significant association with ACL injury risk, whereas weather variables of high evaporation and low prior rainfall showed univariate association with injury risk but could not be entered into a logistic regression equation.Rye grass appears to offer protection against ACL injury compared with bermuda (couch) grass fields. The likely mechanism is reduced "trapping" of football boots by less thatch. Grass species as a single consideration cannot fully explain the ACL early season bias, but is probably responsible for the warm season bias seen in the AFL. Weather variables previously identified as predictors are probably markers for predominance of bermuda over rye grass in mixed fields.
Using Whole-Exome Sequencing to Identify Inherited Causes of Autism
Authors: Timothy W. Yu, Maria H. Chahrour, Michael E. Coulter, Sarn Jiralerspong, Kazuko Okamura-Ikeda, Bulent Ataman, Klaus Schmitz-Abe, David A. Harmin, Mazhar Adli, Athar N. Malik, Alissa M. D’Gama, Elaine T. Lim, Stephan J. Sanders, Ganesh H. Mochida, Jennifer N. Partlow, Christine M. Sunu, Jillian M. Felie, Jacqueline Rodriguez, Ramzi H. Nasir, Janice Ware, Robert M. Joseph, R. Sean Hill, Benjamin Y. Kwan, Muna Al-Saffar, Nahit M. Mukaddes, Asif Hashmi, Soher Balkhy, Generoso G. Gascon, Fuki M. Hisama, Elaine LeClair, Annapurna Poduri, Ozgur Oner, Samira Al-Saad, Sadika A. Al-Awadi, Laila Bastaki, Tawfeg Ben-Omran, Ahmad S. Teebi, Lihadh Al-Gazali, Valsamma Eapen, Christine R. Stevens, Leonard Rappaport, Stacey B. Gabriel, Kyriacos Markianos, Matthew W. State, Michael E. Greenberg, Hisaaki Taniguchi, Nancy E. Braverman, Eric M. Morrow, Christopher A. Walsh
Journal: Neuron (2013)
Companion diagnostic development and commercialization: The good, the bad, and the ugly
Authors: David Jackson
Journal: Clinical Cancer Research (2010)

Abstract QIAGEN (formerly DxS Ltd) has established itself as the market leader in the successful co-development of drug-diagnostic solutions with pharmaceutical partners. QIAGEN has a considerable portfolio of over 15 ongoing collaborations with drug giants such as Amgen, AstraZeneca, Bristol-Myers Squibb and ImClone Systems, Pfizer and Boehringer Ingelheim. This presentation will outline the current state of companion diagnostics as a driver of personalized healthcare; investigate the regulatory and commercial hurdles involved in bringing a companion diagnostic to market and the importance of pharma partnering during clinical development as a way to overcome these hurdles, as well as discuss some of the challenges inherent to companion diagnostic partnerships. Focusing on two of QIAGEN's key experiences with companion diagnostic development for cancer, the presentation will look first at the KRAS story and the challenge of producing the first companion diagnostic of its kind — the TheraScreen®: K-RAS Mutation Kit to predict patient response to metastatic colorectal cancer therapies Vectibix® (Amgen) and Erbitux® (BMS/Imclone Systems) based on the mutation status of the KRAS oncogene. Next, it will examine the importance of another companion diagnostic, the TheraScreen: EGFR29 Mutation Test Kit and its role in facilitating the marketing approval of AstraZeneca's non-small cell lung cancer drug IRESSA® in Europe for EGFR mutation positive patients. With the global perspective on personalized healthcare shifting and pharma recognizing the importance of independent partners for the co-development of drug and diagnostic, the obstacles to bringing companion diagnostic tests to market have shifted. While victories have been won winning the hearts and minds of drug companies, regulators and physicians in key markets like oncology, we are now fighting for value-based reimbursement so that predictive tests can be made available patients and expand the utility of companion diagnostics to new therapeutic areas. The personalized healthcare landscape is set to continue its rapid evolution to meet these new challenges.
<i>BRAF-KIAA1549</i> Fusion Predicts Better Clinical Outcome in Pediatric Low-Grade Astrocytoma
Authors: Cynthia Hawkins, Erin Walker, Nequesha Mohamed, Cindy Zhang, Karine Jacob, Margret Shirinian, Noa Alon, Daniel Kahn, Iris Fried, Katrin Scheinemann, Elena Tsangaris, Peter Dirks, Robert Tressler, Eric Bouffet, Nada Jabado, Uri Tabori
Journal: Clinical Cancer Research (2011)

Recent studies have revealed that the majority of pediatric low-grade astrocytomas (PLGA) harbor the BRAF-KIAA1549 (B-K) fusion gene resulting in constitutive activation of the RAS/MAPK pathway. However, the clinical significance of this genetic alteration is yet to be determined. We aimed to test the prognostic role of the B-K fusion in progression of incompletely resected PLGA.We retrospectively identified 70 consecutive patients with incompletely resected "clinically relevant" PLGA. We added 76 tumors diagnosed at our institution between 1985 and 2010 as controls. We examined BRAF alterations by reverse transcriptase PCR, FISH, and single-nucleotide polymorphism array analysis and correlated that with progression-free survival (PFS).Overall, 60% of tumors were B-K fusion positive. All patients with B-K fused PLGA are still alive. Five-year PFS was 61% ± 8% and 18% ± 8% for fusion positive and negative patients, respectively (P = 0.0004). B-K fusion resulted in similarly significant favorable PFS for patients who received chemotherapy. Multivariate analysis revealed that B-K fusion was the most significant favorable prognostic factor in incompletely resected PLGA and was independent of location, pathology, and age. In vitro, BRAF overexpression resulted in growth arrest associated with DNA damage (γH2AX expression). Five-year PFS was 68% ± 15% and 0% for patients with B-K fused and γH2AX-expressing PLGA versus negative tumors (P = 0.001).These data suggest that B-K fusion confers a less aggressive clinical phenotype on PLGA and may explain their tendency to growth arrest. Combined analysis of B-K fusion and γH2AX expression can determine prognosis and may be a powerful tool to tailor therapy for these patients.
Domiciliary care for smoking related illness costs 1bn a year in England
Authors: A. O'Dowd
Journal: BMJ (2014)

More than £1bn is being spent on domiciliary care each year in England because of the effects of smoking, concludes a new report on the costs in social care arising from the habit.

The report, published by the charity Action on Smoking and Health (ASH) on 3 September,1 found that local councils in England had an average annual bill of more than £600m [€760m; $1bn] a year to help people with smoking related illnesses stay in their own homes (domiciliary care). At the same time individuals also faced a bill of about £450m to cover the cost of their care.

ASH commissioned the economist Howard …
Further Studies on Karyotypes of a Variety of Primary and Transplanted Mouse Polyoma Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: K. E. Hellström, I. Hellström, H. O. Sjögren
Journal: JNCI Journal of the National Cancer Institute (1963)

Karyologic studies were made on 5 primary and 18 transplanted tumors induced by polyoma virus in mice. Sixteen tumors were characterized by stemlines, which were changed chromosomally and most often different for each neoplasm, while 7 tumors, 1 of which was primary, contained cells with the normal diploid number of 40 as their stemline and did not show any detectable structural modifications. Four diploid tumors, followed through several passages, became aneuploid. On the other hand, aneuploid stemlines generally remained constant during prolonged propagation in vivo. All tumors varied considerably around the stemline chromosome numbers. The results show that such chromosomal changes cytologically detectable in telocentric mouse chromosomes are not prerequisite for the neoplastic transformation by the polyoma virus, but apparently often give the cells selective advantage. No systematic chromosome changes distinguished polyoma tumors from tumors where no viral etiology is known.
Indirekte Bulboskopie mit dem Standardtyp des gastroduodenalen Fibroskopes (ACMI) in der Diagnostik des Ulcus bulbi duodeni
Authors: A. Dvorský
Journal: Endoscopy (1969)

1. The proposed imdirect bulboscopy by means of the standard type of gastroduodenal fiberscope (ACMI) rests on the observation of the bulbal cavity through the opening of the pyloric canal. The instrument lies in the distal part of the antrum.
Alcohol, Low-Methionine-Low-Folate Diets, and Risk of Colon Cancer in Men
Authors: E. Giovannucci, E. B. Rimm, A. Ascherio, M. J. Stampfer, G. A. Colditz, W. C. Willett
Journal: JNCI Journal of the National Cancer Institute (1995)

Background: Methylation of DNA, which may have a role in the regulation of gene expression, depends on dietary folate and methionine. Because aberrant DNA methylation may contribute to the initiation or progression of colon cancer, we hypothesized that deficient intakes of folate or methionine and high consumption of alcohol, an antagonist of methyl-group metabolism, increase risk of colon neoplasia. Previously, a high-alcohol and low-methionine-low-folate (methyl-deficient) diet was shown to be related to a higher risk of colon adenomas, precursors of cancer. Purpose: Our goal was to determine if ingestion of a high-alcohol, methyl-deficient diet is related directly to risk of colon cancer. Methods: We assessed dietary intake for a 1-year period for a cohort of 47 931 U.S. male health professionals, 40.75 years old and free of diagnosed cancer in 1986. We assessed diet by using a validated, semiquantitative food-frequency questionnaire. During 6 years of follow-up, we documented 205 new cases of colon cancer in this cohort. Results: Current alcohol intake was directly related to risk of colon cancer (multivariate relative risk [RR] = 2.07; 95% confidence interval [CI] = 1.29–3.32, for >2 drinks versus <0.25 drink daily; P trend = .005), and past drinkers were also at higher risk (RR = 1.95; 95% CI = 1.22–3.10). Individually, folate and methionine intakes were weakly inversely associated with risk of colon cancer. An adverse effect of a high-alcohol, low-methyl diet was not observed among regular users of aspirin, who have previously been shown to be at lower risk for colon cancer. Combinations of high alcohol and low methionine and folate intakes yielded striking associations for total colon cancer (RR = 3.30 [95% CI = 1.58–6.88] comparing high-methyl diets with low-methyl diets among nonusers of aspirin) and for cancers of the distal colon (RR = 7.44; 95% CI = 1.72–32.1). Among men with high intakes of folate or methionine, alcohol levels of >2 drinks daily were not associated with risk of colon cancer. The increased risk of colon cancer associated with alcohol and methyl-deficient diets was not confounded by smoking; intakes of fat, red meat, and fiber; level of physical activity; multivitamin or aspirin use; and body mass index. Conclusions: These findings support the hypothesis that sub-stantial consumption of alcohol, when combined with inadequate intakes of folate and methionine, may increase risk of colon cancer and confirm similar findings in adenomas. Implications: These data provide further support of recommendations to avoid excess alcohol consumption and to increase dietary folate to lower the risk of colon cancer. [J Natl Cancer Inst 87: 265-273, 1995]