tbuckley/cabot-search huggingface dataset:
Cancer as a Complex Phenotype: Pattern of Cancer Distribution within and beyond the Nuclear Family
Authors: Laufey T Amundadottir, Sverrir Thorvaldsson, Daniel F Gudbjartsson, Patrick Sulem, Kristleifur Kristjansson, Sigurdur Arnason, Jeffrey R Gulcher, Johannes Bjornsson, Augustine Kong, Unnur Thorsteinsdottir, Kari Stefansson
Journal: PLoS Medicine (2004)

Background The contribution of low-penetrant susceptibility variants to cancer is not clear. With the aim of searching for genetic factors that contribute to cancer at one or more sites in the body, we have analyzed familial aggregation of cancer in extended families based on all cancer cases diagnosed in Iceland over almost half a century. Methods and Findings We have estimated risk ratios (RRs) of cancer for first- and up to fifth-degree relatives both within and between all types of cancers diagnosed in Iceland from 1955 to 2002 by linking patient information from the Icelandic Cancer Registry to an extensive genealogical database, containing all living Icelanders and most of their ancestors since the settlement of Iceland. We evaluated the significance of the familial clustering for each relationship separately, all relationships combined (first- to fifth-degree relatives) and for close (first- and second-degree) and distant (third- to fifth-degree) relatives. Most cancer sites demonstrate a significantly increased RR for the same cancer, beyond the nuclear family. Significantly increased familial clustering between different cancer sites is also documented in both close and distant relatives. Some of these associations have been suggested previously but others not. Conclusion We conclude that genetic factors are involved in the etiology of many cancers and that these factors are in some cases shared by different cancer sites. However, a significantly increased RR conferred upon mates of patients with cancer at some sites indicates that shared environment or nonrandom mating for certain risk factors also play a role in the familial clustering of cancer. Our results indicate that cancer is a complex, often non-site-specific disease for which increased risk extends beyond the nuclear family.
Investigation of molecular interaction within biological macromolecular complexes by mass spectrometry
Authors: Satoko Akashi
Journal: Medicinal Research Reviews (2006)

Abstract The advent of electrospray ionization (ESI) and matrix‐assisted laser desorption ionization (MALDI) has accelerated structural studies of biological macromolecular complexes. At present, mass spectrometry can provide accurate mass values not only of individual biological macromolecules but also of their assemblies. Furthermore, it can also give information on the interface sites of the biological macromolecular complexes. The present article focuses on the role of mass spectrometry in the investigation of biological molecular interactions, such as protein–protein, protein–DNA, and protein–ligand interactions, which play essential roles in various biological events. © 2006 Wiley Periodicals, Inc.
Hepatitis G virus infection in primary Sjogren's syndrome: analysis in a series of 100 patients
Authors: J. Font, D. Tassies, M. Garcia-Carrasco, M. Ramos-Casals, R. Cervera, J. C. Reverter, J. M. Sanchez-Tapias, R. Mazzara, M. Ingelmo
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To determine the prevalence and clinical significance of hepatitis G virus (HGV) infection in a large cohort of patients with primary Sjögren's syndrome (SS). <h3>PATIENTS AND METHODS</h3> The study included 100 consecutive patients (92 female and eight male), with a mean age of 62 years (range 31–80) that were prospectively visited in our unit. All patients fulfilled the European Community criteria for SS and underwent a complete history, physical examination, as well as biochemical and immunological evaluation for liver disease. Two hundred volunteer blood donors were also studied. The presence of HGV-RNA was investigated in the serum of all patients and donors. Aditionally, HBsAg and antibodies to hepatitis C virus were determined. <h3>RESULTS</h3> Four patients (4%) and six volunteer blood donors (3%) presented HGV-RNA sequences in serum. HGV infection was associated with biochemical signs of liver involvement in two (50%) patients. When compared with primary SS patients without HGV infection, no significant differences were found in terms of clinical or immunological features. HCV coinfection occurs in one (25%) of the four patients with HGV infection. <h3>CONCLUSION</h3> The prevalence of HGV infection in patients with primary SS is low in the geographical area of the study and HCV coinfection is very uncommon. HGV infection alone does not seen to be an important cause of chronic liver injury in the patients with primary SS in this area.
Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients.
Authors: C B Treasure, S V Manoukian, J L Klein, J A Vita, E G Nabel, G H Renwick, A P Selwyn, R W Alexander, P Ganz
Journal: Circulation Research (1992)

Hypertension is a risk factor for coronary atherosclerosis possibly via an adverse effect on the vascular endothelium. Endothelium-mediated relaxation is impaired in animal models of hypertension. However, the effects of hypertension on human coronary artery endothelial cell function are unknown. To test whether endothelium-mediated relaxation is impaired in the coronary arteries of patients with hypertension, we studied 14 patients with essential hypertension requiring therapy and 15 nonhypertensive control patients undergoing cardiac catheterization. All had angiographically normal, smooth-appearing coronary arteries. Patients were matched for age and other coronary atherosclerosis risk factors. To assess endothelial cell function, the endothelium-dependent vasodilator acetylcholine (ACh, 0.01, 0.1, and 1.0 microM) and the endothelium-independent vasodilator nitroglycerin (40 micrograms) were selectively infused into the left anterior descending or circumflex coronary artery. Diameter change (expressed as percent) was assessed using quantitative angiography. There was a marked vasoconstrictor response to serial doses of ACh in hypertensive patients (-7%, -21%, and -27%) compared with control patients (-4%, -5%, and -7%) (p less than 0.02). The vasodilator response to nitroglycerin was preserved in hypertensive patients (+29%) and control patients (+25%) (p = NS), suggesting that endothelial cell dysfunction accounted for the differences in response to ACh. Thus, patients with hypertension have an accentuated coronary vasoconstrictor response to ACh, suggesting that endothelium-mediated regulation of coronary vascular tone is impaired by essential hypertension. This may reflect more generalized coronary endothelial changes contributing to the pathogenesis of atherosclerosis as well as hypertension.
Mixing Insulin Aspart With Detemir Does Not Affect Glucose Excursion in Children With Type 1 Diabetes
Authors: Thanh M. Nguyen, Venkat S. Renukuntla, Rubina A. Heptulla
Journal: Diabetes Care (2010)

OBJECTIVE We hypothesized that insulin detemir mixed with aspart had equivalent effects on blood glucose as if being given as separate injections in pediatric type 1 diabetes patients. RESEARCH DESIGN AND METHODS Fourteen children with type 1 diabetes were randomly assigned to either Study A (mixed insulins) or Study B (separate insulins) for the first 10 days and crossed over for the last 10 days. Each subject underwent continuous glucose monitoring on the last 72 h of each study. RESULTS The 48-h area under the curve (mmol/hour/l), M-value, and mean amplitude of glucose excursion (mmol/l) for Study A versus Study B were 457 ± 70 versus 469 ± 112 (P = 0.58), 39.67 ± 15.37 versus 39.75 ± 9.69 (P = 0.98), and 6.35 ± 1.92 versus 5.98 ± 0.92 (P = 0.42), respectively. CONCLUSIONS Insulin detemir mixed with aspart had equivalent effects on blood glucose versus giving them as separate injections in children with type 1 diabetes.
Laparoendoscopic Single-site Nephrectomy Compared with Conventional Laparoscopic Nephrectomy: A 5-year, Single-surgeon Experience
Authors: Jodi A. Antonelli, Aditya Bagrodia, Christopher Odom, Ephrem O. Olweny, Steven Faddegon, Jeffrey A. Cadeddu
Journal: European Urology (2013)
Anergy to dinitrochlorobenzene and depression of T-lymphocytes in Crohn's disease and ulcerative colitis.
Authors: S Meyers, D B Sacher, R N Taub, H D Janowitz
Journal: Gut (1976)

Skin reactivity to dinitrochlorobenzene (DNCB) and levels of circulating T-lymphocytes were measured in 15 patients with ulcerative colitis, 15 patients with Crohn9s disease, and 12 normal control subjects. Diminished reactivity to DNCB was demonstrated in 87% of patients with Crohn9s disease (P less than 0-001) and in 53% with ulcerative colitis (P less than 0-02), as compared with only 8-5% of controls; anergy was more frequent in Crohn9s disease than in ulcerative colitis (P less than 0-05). Levels of circulating T-lymphoctes were also depressed in both Crohn9s disease and ulcerative colitis (P less than 0-001) as compared with controls, with the values lower in Crohn9s disease than in ulcerative colitis (P less than 0-02). There were no correlations of DNCB response with extent, duration, or severity of disease nor with T-cell levels within any patient group. These data provide further support for the concept that there is impairment of cell-mediated immunity among many patients with chronic inflammatory bowel disease, including both Crohn9s disease and ulcerative colitis.
Programmable insect cell carriers for systemic delivery of integrated cancer biotherapy
Authors: D.G. Roy, A.T. Power, M.C. Bourgeois-Daigneault, T. Falls, L. Ferreira, A. Stern, C. Tanese de Souza, J.A. McCart, D.F. Stojdl, B.D. Lichty, H. Atkins, R.C. Auer, J.C. Bell, F. Le Boeuf
Journal: Journal of Controlled Release (2015)
Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma
Authors: Assunta De Rienzo, Michael A. Archer, Beow Y. Yeap, Nhien Dao, Daniele Sciaranghella, Antonios C. Sideris, Yifan Zheng, Alexander G. Holman, Yaoyu E. Wang, Paola S. Dal Cin, Jonathan A. Fletcher, Renee Rubio, Larry Croft, John Quackenbush, Peter E. Sugarbaker, Kiara J. Munir, Jesse R. Battilana, Corinne E. Gustafson, Lucian R. Chirieac, Soo Meng Ching, James Wong, Liang Chung Tay, Stephen Rudd, Robert Hercus, David J. Sugarbaker, William G. Richards, Raphael Bueno
Journal: Cancer Research (2015)

Abstract Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P &amp;lt; 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepitheliod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM. Cancer Res; 76(2); 319–28. ©2015 AACR.
The size and number of bone marrow megakaryocytes in malignant lymphoma and their relationship to abnormalities in platelet count
Authors: A. M. Gladwin, J. F. Martin, E. A. Trowbridge, D. N. Slater, D. Reardon
Journal: American Journal of Hematology (1990)

Abstract Platelet counts were measured routinely in 718 volunteer blood donors and 124 patients with malignant lymphoma. When considered by gender, the mean platelet counts of the patients with malignant lymphoma were significantly increased when compared to controls ( P &lt; 0.01). In addition, 9% of males and 4% of females with lymphoma exhibited a thrombocytosis, in which their platelet counts exceeded the upper limit of the normal platelet count for control subjects (defined as 2 SDs in excess of the mean value). Megakaryocyte whole size, cytoplasmic and nuclear sizes, and megakaryocyte numbers were also quantified in bone marrow obtained from the iliac crest of 5 hematologically normal subjects and 26 patients with malignant lymphoma. Mean megakaryocyte sizes were significantly greater in subjects with lymphoma, when compared to control values ( P &lt; 0.05). No significant differences in megakaryocyte numbers in bone marrow were observed between the two groups. For subjects with malignant lymphoma, platelet count was found to be significantly positively correlated with megakaryocyte size. The results of this study suggest that the elevated platelet count associated with malignant lymphoma is mediated by an increase in the size of the megakaryocytes in the bone marrow.
Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial
Authors: F Verdon
Journal: BMJ (2003)

To determine the subjective response to iron therapy in non-anaemic women with unexplained fatigue.Double blind randomised placebo controlled trial.Academic primary care centre and eight general practices in western Switzerland.144 women aged 18 to 55, assigned to either oral ferrous sulphate (80 mg/day of elemental iron daily; n=75) or placebo (n=69) for four weeks.Level of fatigue, measured by a 10 point visual analogue scale.136 (94%) women completed the study. Most had a low serum ferritin concentration; <or= 20 microg/l in 69 (51%) women. Mean age, haemoglobin concentration, serum ferritin concentration, level of fatigue, depression, and anxiety were similar in both groups at baseline. Both groups were also similar for compliance and dropout rates. The level of fatigue after one month decreased by -1.82/6.37 points (29%) in the iron group compared with -0.85/6.46 points (13%) in the placebo group (difference 0.95 points, 95% confidence interval 0.32 to 1.62; P=0.004). Subgroups analysis showed that only women with ferritin concentrations <or= 50 microg/l improved with oral supplementation.Non-anaemic women with unexplained fatigue may benefit from iron supplementation. The effect may be restricted to women with low or borderline serum ferritin concentrations.
Short-term health effects of particulate and photochemical air pollution in asthmatic children
Authors: J. Just, C. Ségala, F. Sahraoui, G. Priol, A. Grimfeld, F. Neukirch
Journal: European Respiratory Journal (2002)

In a previous panel study in Paris, France, detrimental effects of moderately high levels of winter air pollution on the symptoms and lung function of asthmatic children were demonstrated. A new study was conducted, with the aim of assessing the short-term effects of photo-oxidant and particulate air pollution on childhood asthma during spring and early summer in Paris. Eighty-two medically diagnosed asthmatic children were followed up for 3 months. Outcomes included the incidence and prevalence of asthma attacks, nocturnal cough, supplementary use of β 2 -agonists, symptoms of airway irritation, and peak expiratory flow (PEF) value and its variability. The statistical methods controlled for the lack of independence between daily health outcomes, temporal trends and pollen and weather conditions. Black smoke and nitrogen dioxide (NO 2 ) were associated with increases in the occurrence of nocturnal cough and respiratory infections. Ozone (O 3 ) was associated with an increase in the occurrence of asthma attacks and respiratory infections and with changes in lung function, as shown by an increase in PEF variability and a decrease in PEF. Statistically significant interactions were demonstrated between O 3 and temperature and between O 3 and pollen count for asthma attacks. O 3 levels had a greater effect on additional bronchodilator use and on irritations of the eyes, nose and throat on days on which no steroids were used. Particulate matter was associated with eye irritation only. This study showed that, although within international air quality standards, the prevailing levels of photo-oxidant and particulate pollution in spring and early summer had measurable short-term effects on children with mild-to-moderate asthma.
Inhibition of sphincter of Oddi function by the nitric oxide carrier S-nitroso-N-acetylcysteine in rabbits and humans.
Authors: A Slivka, R Chuttani, D L Carr-Locke, L Kobzik, D S Bredt, J Loscalzo, J S Stamler
Journal: Journal of Clinical Investigation (1994)

Nitric oxide (NO) is an inhibitor of gastrointestinal smooth muscle. Model systems of the gut predict the NO will complex with biological thiol (SH) groups, yielding S-nitrosothiols (RS-NO), which may limit the propensity to form mutagenic nitrosamines. The inhibitory effects of NO and its biologically relevant adducts on sphincter of Oddi (SO) motility have been inferred from animal studies; however, their importance in regulating human SO is not known. The objectives of this study were to (a) provide histologic confirmation of nitric oxide synthase (NOS) in human SO; (b) characterize the pharmacology of S-nitroso-N-acetylcysteine (SNAC), an exemplary S-nitrosothiol, on SO motility in a rabbit model; and (c) study the effects of topical SNAC on SO motility in humans. Immunocytochemical and histochemical identification of NOS was performed in human SO. The pharmacologic response of SNAC was defined in isolated rabbit SO using a standard bioassay. Topical SNAC was then applied to the duodenal papilla in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and biliary manometry. NOS was localized to nerve fibers and bundles of the SO in rabbits and humans. SNAC inhibited spontaneous motility (frequency and amplitude) as well as acetylcholine-induced elevations in SO basal pressure in the rabbit model. In patients undergoing ERCP and biliary manometry, topical SNAC inhibited SO contraction freqency, basal pressure, and duodenal motility. NOS is localized to neural elements in human SO, implicating a role for NO in regulating SO function. Supporting this concept, SNAC is an inhibitor of SO and duodenal motility when applied topically to humans during ERCP. Our data suggest a novel clinical approach using local NO donors to control gastrointestinal motility and regulate sphincteric function.
Studying the relationship between dreaming and sleep-dependent memory processes: Methodological challenges
Authors: Michael Schredl
Journal: Behavioral and Brain Sciences (2013)

The hypothesis that dreaming is involved in off-line memory processing is difficult to test because major methodological issues have to be addressed, such as dream recall and the effect of remembered dreams on memory. It would be fruitful--in addition to studying the ancient art of memory (AAOM) in a scanner--to study the dreams of persons who use AAOM regularly.
Soluble guanylate cyclase stimulators as a potential therapy for PAH: enthusiasm, pragmatism and concern
Authors: E. D. Michelakis
Journal: European Respiratory Journal (2009)

Despite recent progress, pulmonary arterial hypertension (PAH) remains without a cure. The impact of the approved drugs on PAH is small and, with the exception of some parenteral therapies, they have little or uncertain effects on haemodynamics, right ventricular (RV) function and survival.

There are two main reasons for this. First, the complexity of this vascular remodelling disease is high and its pathology includes fundamental mechanisms from several other diseases and syndromes, including neoplasia (the anti-apoptotic and pro-proliferative remodelling within the vessel wall), degenerative diseases (the early loss of endothelial cells and microvessels) and inflammation 1. In addition, a reversal of vascular remodelling will mean little unless it is accompanied by a reversal of RV failure, which at this point remains clinically unpredictable. Secondly, whatever therapy is developed, it needs to be directed against the unique features of PAH and should be selective for the pulmonary circulation, sparing the often normal systemic vessels 1. This second factor is perhaps the most challenging. One of the common features of all existing therapies for PAH is that they were originally developed for systemic vascular diseases and it was only after they either failed or determined to be non-profitable, that they were tested on PAH.

Surprisingly, there are several quite promising therapies for PAH which remain untested in humans. One of the main reasons is the lack of continuity and the poor efficiency in translational research 1. Typically, one team might perform cellular work, another small animal work, another large animal work and another phase 1 trials, before phase 2 and 3 trials are planned. This usually takes many years.

In the current issue of the European Respiratory Journal ( ERJ ) 2 and a very recent issue of the ERJ 3, the same team from Giessen (Germany), in collaboration with …
Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: a Japanese Gynecologic Oncology Group study (JGOG2041)
Authors: H. Nomura, D. Aoki, F. Takahashi, N. Katsumata, Y. Watanabe, I. Konishi, T. Jobo, M. Hatae, M. Hiura, N. Yaegashi
Journal: Annals of Oncology (2010)
Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial
Authors: Stanley J Szefler, Herman Mitchell, Christine A Sorkness, Peter J Gergen, George T O'Connor, Wayne J Morgan, Meyer Kattan, Jacqueline A Pongracic, Stephen J Teach, Gordon R Bloomberg, Peyton A Eggleston, Rebecca S Gruchalla, Carolyn M Kercsmar, Andrew H Liu, Jeremy J Wildfire, Matthew D Curry, William W Busse
Journal: The Lancet (2008)