tbuckley/cabot-search huggingface dataset:
Efficient Tumor Suppression by Glioma-Specific Murine Cytotoxic T Lymphocytes Transfected With Interferon- Gene
Authors: S.-i. Miyatake, K. Nishihara, H. Kikuchi, J. Yamashita, Y. Namba, M. Hanaoka, Y. Watanabe
Journal: JNCI Journal of the National Cancer Institute (1990)

We have recently shown that exogenous expression of the mouse interferon-γ (IFN-γ) gene augmented the cell-killing potential of a line of cytotoxic T lymphocytes (CTLs) specific against a murine glioma line (203-glioma). In the present work, we further investigated the in vivo antitumor effects of the E7–6 and Ey-9 sublines of this CTL line transfected with the IFN-ygene. Using the Winn assay to test the neutralization of subcutaneous gliomas, we determined that these CTL sublines were more effective than the E-4 parent CTL line and that suppression of the tumor growth was dependent on the number of effector cells (CTLs). Moreover, intravenous injection of Ey-9 cells was more effective in suppressing the tumor growth than intravenous injection of E-4 cells. These results suggest that transfection of anti-tumor effector cells with the IFN-y gene could improve the efficacy of adoptive immunotherapy against cancer. [J Natl Cancer Inst 82: 217–220, 1990]
Effect of Epinephrine, Norepinephrine and Serotonin Upon Systemic Small and Large Vessel Resistance
Authors: F. J. HADDY, M. FLEISHMAN, D. A. EMANUEL, J. B. Scott
Journal: Circulation Research (1957)

Locally injected epinephrine and norepinephrine elevate dog foreleg total vascular resistance primarily through small vessel constriction. Serotonin does not significantly change total resistance, constricts large arteries and veins and dilates small vessels.
Association of variation in Fc receptor 3B gene copy number with rheumatoid arthritis in Caucasian samples
Authors: C. McKinney, M. Fanciulli, M. E. Merriman, A. Phipps-Green, B. Z. Alizadeh, B. P. C. Koeleman, N. Dalbeth, P. J. Gow, A. A. Harrison, J. Highton, P. B. Jones, L. K. Stamp, S. Steer, P. Barrera, M. J. H. Coenen, B. Franke, P. L. C. M. van Riel, T. J. Vyse, T. J. Aitman, T. R. D. J. Radstake, T. R. Merriman
Journal: Annals of the Rheumatic Diseases (2010)

There is increasing evidence that variation in gene copy number (CN) influences clinical phenotype. The low-affinity Fcgamma receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment to sites of inflammation and activation of polymorphonuclear neutrophils (PMNs). Given recent evidence that low FCGR3B CN is a risk factor for systemic but not organ-specific autoimmune disease and the potential importance of PMN in the pathophysiology of rheumatoid arthritis (RA), the authors hypothesised that FCGR3B gene dosage influences susceptibility to RA.
RhoC is a major target of microRNA-93-5P in epithelial ovarian carcinoma tumorigenesis and progression
Authors: Xi Chen, Shuo Chen, Yin-Ling Xiu, Kai-Xuan Sun, Zhi-Hong Zong, Yang Zhao
Journal: Molecular Cancer (2015)

An increasing amount of evidence has revealed that microRNAs regulate various biological processes, including cell differentiation, cell proliferation, apoptosis, drug resistance, and fat metabolism. Studies have shown that miR-93's targetome in cancer has not been fully defined. Moreover, the role of miR-93 in epithelial ovarian carcinoma (EOC) remains largely unknown.MIR-93 mRNA expression in normal ovarian tissue, benign tumors, borderline tumors, primary ovarian carcinomas, and metastatic omentum was quantified. The ovarian carcinoma cell lines OVCAR3, SKOV3/DDP, and HO8910-PM were transfected with miR-93-5P, after which cell phenotype and expression of relevant molecules were assayed. Dual-luciferase reporter assay and a xenograft mouse model were used to examine miR-93 and its target gene RHOC (Ras homolog gene family member C).MIR-93 mRNA expression was significantly lower in ovarian carcinomas and borderline tumors than in normal ovarian tissues (p < 0.05), and was lower in metastatic omentum than in relative primary ovarian carcinomas (p < 0.05). MIR-93 mRNA expression was also negatively associated with differentiation (well vs. poor and moderate) and International Federation of Gynecology and Obstetrics staging (FIGO stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05), besides, miR-93 was higher expressed in mucinous adenocarcinoma than the other types (p < 0.05). MiR-93-5P overexpression reduced proliferation (p < 0.05); promoted G1 or S arrest and apoptosis (p < 0.05); suppressed migration and invasion (p < 0.05); and reduced RhoC, P70S6 kinase, Bcl-xL, matrix metalloproteinase 9 (MMP9) mRNA or protein expression; conversely, it induced P53 and cleaved PARP expression (p < 0.05). Dual-luciferase reporter assay indicated that miR-93 directly targeted RhoC by binding its 3' untranslated region. MiR-93-5P transfection also suppressed tumor development and RhoC expression (determined by immunohistochemistry) in vivo in the xenograft mouse model (p < 0.05).This is the first demonstration that miR-93-5P may inhibit EOC tumorigenesis and progression by targeting RhoC. These findings indicate that miR-93-5P is a potential suppressor of ovarian cellular proliferation. The involvement of miR-93-5P-mediated RhoC downregulation in inhibiting EOC aggressiveness may provide extended insight into the molecular mechanisms underlying cancer aggressiveness.
Gene Expression Levels Are a Target of Recent Natural Selection in the Human Genome
Authors: S. Kudaravalli, J.-B. Veyrieras, B. E. Stranger, E. T. Dermitzakis, J. K. Pritchard
Journal: Molecular Biology and Evolution (2008)

Changes in gene expression may represent an important mode of human adaptation. However, to date, there are relatively few known examples in which selection has been shown to act directly on levels or patterns of gene expression. In order to test whether single nucleotide polymorphisms (SNPs) that affect gene expression in cis are frequently targets of positive natural selection in humans, we analyzed genome-wide SNP and expression data from cell lines associated with the International HapMap Project. Using a haplotype-based test for selection that was designed to detect incomplete selective sweeps, we found that SNPs showing signals of selection are more likely than random SNPs to be associated with gene expression levels in cis. This signal is significant in the Yoruba (which is the population that shows the strongest signals of selection overall) and shows a trend in the same direction in the other HapMap populations. Our results argue that selection on gene expression levels is an important type of human adaptation. Finally, our work provides an analytical framework for tackling a more general problem that will become increasingly important: namely, testing whether selection signals overlap significantly with SNPs that are associated with phenotypes of interest.
Promoter Hypermethylation of Hallmark Cancer Genes in Atypical Adenomatous Hyperplasia of the Lung
Authors: Julien D.F. Licchesi, William H. Westra, Craig M. Hooker, James G. Herman
Journal: Clinical Cancer Research (2008)

Abstract Purpose: According to current models of tumorigenesis, the progression of phenotypic changes culminating in overtly malignant carcinoma is driven by genetic and epigenetic alterations. The recognition of an early form of glandular neoplasia termed atypical adenomatous hyperplasia (AAH), a precursor lesion from which lung adenocarcinomas arise, provides an opportunity for characterizing early epigenetic alterations involved in lung tumorigenesis. Experimental Design: We evaluated AAHs, adjacent normal lung tissue, and synchronous lung adenocarcinomas for promoter hypermethylation of genes implicated in lung tumorigenesis (p16, TIMP3, DAPK, MGMT, RARβ, RASSF1A, and hTERT). Results: For individual genes and the number of genes methylated, we observed a significant increase in the frequency of promoter hypermethylation in the histologic progression from normal to AAH, with low-grade or high-grade atypia, and finally to adenocarcinoma (Ptrend ≤ 0.01). Multifocal AAHs from individual patients had distinct patterns of promoter hypermethylation, suggesting divergent epigenetic field defects. There were statistically significant positive associations for the presence of promoter hypermethylation of individual and multiple genes with advanced histology, with odds ratios between 4.3 and 58.5. p16 conveyed the strongest individual association for promoter hypermethylation when comparing tumor or high-grade AAH to low-grade AAH or normal tissue, with an odds ratio of 45.5 (95% confidence interval, 5.8-360.5). Conclusion: This study shows epigenetic progression in the earliest stages of glandular neoplasia of the lung and has implications for early lung cancer detection.
Lung alkaline phosphatase as a marker of fibrosis in chronic interstitial disorders.
Authors: A Capelli, M Lusuardi, C G Cerutti, C F Donner
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Alkaline phosphatase (ALP) in lung lavage fluids is a marker of tissue damage and type II cell proliferation. Type II pneumocytes are extensively involved in fibrosis. The aim of our study was to verify whether local ALP activity can be held as a marker of fibrosis in chronic interstitial lung disorders. ALP was determined in the bronchoalveolar lavage of 140 subjects: 25 control subjects, and 33 patients with silicosis, 38 with idiopathic pulmonary fibrosis (IPF), and 18 with Stage I, 16 with Stage II, and 10 with Stage III/IV sarcoidosis. We observed a significant augmentation of ALP activity in patients with IPF, as well as in those with Stages II and III/IV sarcoidosis. Albumin was higher in those with Stages I and II sarcoidosis, but it was normal in the other groups. Therefore, a significant increase in ALP:albumin ratio characterized IPF (median, 10.3; range, 2.4 to 83.2) and Stage III/IV sarcoidosis, (8.9, 4.4 to 103.1) as compared with Stage I (2, 1.1 to 18) and Stage II (4.7, 0.7 to 26.6) sarcoidosis, silicosis (6.5, 0.5 to 42.7), and the nonsmoker (6.1, 2.9 to 12.9) and smoker (6.4, 2 to 15.2) control groups. We conclude that an increase of the ALP: albumin ratio in bronchoalveolar lavage fluids from patients with chronic interstitial disorders may reflect a fibrosing progression.
A survey of state medical licensing boards: can the travelling team physician practice in your state?
Authors: Tracey Viola, Chad Carlson, Thomas H Trojian, Jeffrey Anderson
Journal: British Journal of Sports Medicine (2012)

This was a study that surveyed state medical licensing boards in the USA, to see if they have laws or exemptions for travelling team physicians to practice medicine on their own team, while travelling to that state. Surveys were sent to 58 medical boards, with legislative data being obtained for 54. Eighteen states (33%) allow team physicians travelling with their team to practice medicine with their home-state license. Thirty-six states (67%) do not have a legal pathway to allow the practice of medicine without a license: 27 (50%) do not allow the practice of medicine without a license from their state, 6 (11%) have an exemption for a ‘consultant’ to act in concert with a home-state physician (though this is not applicable to the team physician) and 3 (6%) do not have an exemption, but recognise that it happens without their involvement. A second survey was sent to 20 malpractice carriers, identified by an internet search to represent a diverse sample, to see if these companies offered policies that would cover the team physician, and if they also had licensure requirements. Of the 11 that responded, only 2 companies would provide coverage regardless of individual state licensing requirements, 5 companies would provide coverage to a provider who travels, but would require the provider to be licensed in any state they travel to and 4 companies would not provide coverage out of the home state, regardless of licensure. The American Medical Society for Sports Medicine is working on a Federal patch for this problem.
Catabolism of human γG-immunoglobulins of different heavy chain subclasses
Authors: Hans L. Spiegelberg, Ben G. Fishkin, Howard M. Grey
Journal: Journal of Clinical Investigation (1968)

The rates of catabolism of human γG-immunoglobulins of subclasses γG1, γG2, γG3, and γG4 were studied by determining the rates of elimination from the circulation of pairs of 131I-and 125I-labeled γG-myeloma proteins in 57 patients suffering from cancer other than multiple myeloma. On the average, γG1-, γG2-, and γG4-myeloma proteins were catabolized at a rate similar to that of normal γG-immunoglobulin, whereas γG3-myeloma proteins were catabolized more rapidly than normal γG-immunoglobulin. The average half-lives for the myeloma proteins were 12.3 days for normal γG, 11.6 days for γG1, 12.4 days for γG2, 8.2 days for γG3, and 11.3 days for γG4. However, significant differences in catabolic rates were observed when individual myeloma proteins of a single subclass were compared. These individual variations were present within all four heavy chain subclasses. The extent of differences ranged from 10 to 47%. The catabolic rate of normal γG was in an intermediate range when compared with myeloma proteins of relatively long and short half-lives. The rate of catabolism of an individual myeloma protein did not correlate with its light chain type, Gm factor, carbohydrate content, or electrophoretic mobility. These findings indicate that the structure(s) related to the catabolism of γG-immunoglobulins are complex and differ from one immunoglobulin molecule to another.
Prevalence of hepatitis B or C virus infection in patients with fulminant viral hepatitis. An analysis using polymerase chain reaction
Authors: Kaoru Inokuchi, Keisuke Nakata, Keisuke Hamasaki, Manabu Daikoku, Kazuhiko Nakao, Yuji Kato, Hiroshi Yatsuhashi, Michiaki Koga, Michitami Yano, Shigenobu Nagataki
Journal: Journal of Hepatology (1996)
Urocortin II enhances contractility in rabbit ventricular myocytes via CRF2 receptor-mediated stimulation of protein kinase A
Authors: L YANG, J KOCKSKAMPER, F HEINZEL, M HAUBER, S WALTHER, J SPIESS, B PIESKE
Journal: Cardiovascular Research (2005)

Urocortin II (UcnII), a peptide of the corticotropin-releasing factor (CRF) family, exerts profound actions on the cardiovascular system. Direct effects of UcnII on adult cardiomyocytes have not been evaluated before. Our aim was to characterize functional effects of UcnII on cardiomyocytes and to elucidate the underlying signaling pathway(s) and cellular mechanisms.Rabbit ventricular cardiomyocytes were stimulated at 0.5 Hz (22-25 degrees C). Unloaded cell shortening (FS, edge detection), [Ca(2+)](i) transients (Fluo-4), and L-type Ca(2+) currents (I(Ca), whole-cell patch clamping) were measured. Sarcoplasmic reticulum (SR) Ca(2+) load was assessed by rapid application of caffeine (20 mmol/L).UcnII increased cell shortening and accelerated relaxation in a time- and concentration-dependent manner (EC(50): 10.7 nmol/L). The inotropic effect of UcnII was maximal at 100 nmol/L (35%+/-11% increase in FS, n=8, P<0.05). The inotropic and lusitropic actions of UcnII were largely eliminated by inhibition of CRF(2) receptors (10 nmol/L antisauvagine-30, n=5) or protein kinase A (PKA, 500 nmol/L H-89, n=5). UcnII increased [Ca(2+)](i) transient amplitude (by 63%+/-35%, n=7, P<0.05) and decreased the time constant for decay (from 800+/-63 to 218+/-27 ms, n=7, P<0.001). UcnII also increased SR Ca(2+) load (by 19%+/-7%, n=7, P<0.05) and fractional Ca(2+) release (from 57%+/-7% to 98%+/-2%, n=7, P<0.01). I(Ca) was augmented by 32.7%+/-10.0% (n=9, P<0.05) and the I(Ca)-V relationship was shifted by -15 mV during UcnII treatment.UcnII exerts positive inotropic and lusitropic effects in cardiomyocytes via CRF(2) receptor-mediated stimulation of PKA which augments I(Ca) and SR Ca(2+) load to increase SR Ca(2+) release and [Ca(2+)](i) transients.
Clonal expansion of a new MLL rearrangement in the absence of leukemia
Authors: Oliver Teuffel, David R. Betts, Marco Thali, Dominique Eberle, Claus Meyer, Björn Schneider, Rolf Marschalek, Luba Trakhtenbrot, Ninette Amariglio, Felix K. Niggli, Beat W. Schäfer
Journal: Blood (2005)
Reappraisal of known malaria resistance loci in a large multicenter study
Authors: Kirk A Rockett, Geraldine M Clarke, Kathryn Fitzpatrick, Christina Hubbart, Anna E Jeffreys, Kate Rowlands, Rachel Craik, Muminatou Jallow, David J Conway, Kalifa A Bojang, Margaret Pinder, Stanley Usen, Fatoumatta Sisay-Joof, Giorgio Sirugo, Ousmane Toure, Mahamadou A Thera, Salimata Konate, Sibiry Sissoko, Amadou Niangaly, Belco Poudiougou, Valentina D Mangano, Edith C Bougouma, Sodiomon B Sirima, David Modiano, Lucas N Amenga-Etego, Anita Ghansah, Kwadwo A Koram, Michael D Wilson, Anthony Enimil, Jennifer Evans, Olukemi Amodu, Subulade Olaniyan, Tobias Apinjoh, Regina Mugri, Andre Ndi, Carolyne M Ndila, Sophie Uyoga, Alexander Macharia, Norbert Peshu, Thomas N Williams, Alphaxard Manjurano, Eleanor Riley, Chris Drakeley, Hugh Reyburn, Vysaul Nyirongo, David Kachala, Malcolm Molyneux, Sarah J Dunstan, Nguyen Hoan Phu, Nguyen Thi Ngoc Quyen, Cao Quang Thai, Tran Tinh Hien, Laurens Manning, Moses Laman, Peter Siba, Harin Karunajeewa, Steve Allen, Angela Allen, Timothy M E Davis, Pascal Michon, Ivo Mueller, Angie Green, Sile Molloy, Kimberly J Johnson, Angeliki Kerasidou, Victoria Cornelius, Lee Hart, Aaron Vanderwal, Miguel SanJoaquin, Gavin Band, Si Quang Le, Matti Pirinen, Nuno Sepúlveda, Chris C A Spencer, Taane G Clark, Tsiri Agbenyega, Eric Achidi, Ogobara Doumbo, Jeremy Farrar, Kevin Marsh, Terrie Taylor, Dominic P Kwiatkowski
Journal: Nature Genetics (2014)
The role of bile salts in controlling the rate of intestinal cholesterogenesis
Authors: John M. Dietschy
Journal: Journal of Clinical Investigation (1968)

According to current concepts, the liver and gastrointestinal tract are considered to be the major, if not the sole, sources of circulating serum cholesterol. While several mechanisms have been described which control the rate of hepatic cholesterogenesis, only biliary diversion is known to alter the rate of sterol synthesis in the intestine. The present study was designed to identify the inhibitory constituent of bile and to define its anatomic and biochemical sites of action. After either biliary diversion or cholestyramine feeding, there is a marked enhancement of cholesterogenesis at every level of the small intestine; this effect is specific for sterol synthesis since acetate incorporation into fatty acids and CO(2) is unaffected by these experimental manipulations. In the present investigation bile salt has been shown to be the constituent of whole bile responsible for the inhibited rate of sterol synthesis found in the intact animal, and in addition, an inverse relationship has been shown to exist between the steady-state intraluminal bile salt concentration and the rate of cholesterogenesis in the adjacent bowel wall. The inhibitory effect of bile salt is directed at the cells of the intestinal crypt, the major anatomic site for sterol synthesis in the small bowel. This feedback inhibition has been localized in the biosynthetic sequence to a step between acetyl CoA and mevalonic acid and, presumably, is at the enzymatic step mediated by hydroxymethylglutaryl reductase. These studies emphasize the close interrelationship which exists between the mechanisms of control of cholesterogenesis in the liver and small intestine. Sterol synthesis in the liver is regulated by exogenous cholesterol intake, whereas the rate of intestinal sterol synthesis is controlled by bile salt, the major end product of the hepatic catabolism of cholesterol.
Gender Differences in Violent Behaviors: Relationship to Clinical Symptoms and Psychosocial Factors
Authors: Menahem Krakowski, Pal Czobor
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Men are more violent than women in the general population, but this has not been found to be the case among psychiatric inpatients. The reason for this exception is poorly understood. The present study investigated gender differences in violent behaviors among patients with major psychiatric disorders. It examined various clinical symptoms and psychosocial factors to determine their differential impact on violence in men and women. METHOD: Physical assaults and verbal assaults committed by psychiatric inpatients were recorded prospectively. Patients whose violent incident occurred during their first 2 months of hospitalization were eligible for the study. Patient history of community violence was also obtained. Psychiatric symptoms and ward behaviors were assessed upon entry into the study and after 4 weeks. RESULTS: A similar percentage of women and men had an incident of physical assault in the hospital. Among the patients entered into the study, the women had a much higher level of verbal assaults throughout the evaluation period and a higher level of early physical assaults (i.e., within the first 10 days of the 4-week study period). Positive psychotic symptoms were more likely to result in assaults in women than in men. Physical assaults in the community, on the other hand, were more common in men and were associated with substance abuse, property crime, and a history of school truancy. CONCLUSIONS: There are gender differences in the patterns of violent behavior among patients with major psychiatric disorders. Furthermore, psychiatric symptoms and psychosocial risk factors have a different impact on this behavior in men and women. This has important implications for the prediction and differential treatment of violent behavior.
Patterns of illness and injury encountered in amateur ocean yacht racing: an analysis of the British Telecom Round the World Yacht Race 1996–1997
Authors: C J S Price, T J W Spalding, C McKenzie
Journal: British Journal of Sports Medicine (2002)

To quantify the incidence and type of medical problem arising during an amateur circumnavigation yacht race, the BT Global Challenge.All cases from 14 participating yachts in a confidential medical log completed by an appointed medic were reported.A total of 685 cases were reported, of which 299 (43.6%) were injuries and 386 (56.4%) illnesses. The subtype of injury, illness, and three evacuations at sea are described.Injury and other forms of medical problem are relatively common in an amateur long distance ocean yacht race. Most can be adequately managed at sea, provided that optimal communication, training, and equipment are provided and maintained.
Results of intracoronary recombinant human vascular endothelial growth factor (rhVEGF) administration trial
Authors: T.D. Henry, K. Rocha-Singh, J.M. Isner, D.J. Kereiakes, F.J. Giordano, M. Simons, D.W. Losordo, R.C. Hendel, R.O. Bonow, J.M. Rothman, E.R. Borbas, E.R. McCluskey
Journal: Journal of the American College of Cardiology (1998)