tbuckley/cabot-search huggingface dataset:
Indian Hedgehog is an antagonist of Wnt signaling in colonic epithelial cell differentiation
Authors: Gijs R van den Brink, Sylvia A Bleuming, James C H Hardwick, Berber L Schepman, G Johan Offerhaus, Josbert J Keller, Corinne Nielsen, William Gaffield, Sander J H van Deventer, Drucilla J Roberts, Maikel P Peppelenbosch
Journal: Nature Genetics (2004)
Disparities in Treatment and Outcome for Renal Cell Cancer Among Older Black and White Patients
Authors: Sonja I. Berndt, H. Ballentine Carter, Mark P. Schoenberg, Craig J. Newschaffer
Journal: Journal of Clinical Oncology (2007)

Black patients with renal cell cancer have shorter survival compared with their white counterparts, but the causes for this disparity are unclear. To elucidate reasons for this inequality, we examined differences in treatment and survival between black and white patients.A retrospective cohort study was conducted using data from the linked Surveillance, Epidemiology and End Results (SEER) cancer registry and Medicare databases. Participants included 964 black and 10,482 white patients age >or= 65 years who were enrolled into Medicare and diagnosed with renal cell cancer between 1986 and 1999. Information on surgical treatment was ascertained from both databases, whereas data regarding coexisting illness and survival was obtained from the Medicare database.The percentage of black patients receiving nephrectomy treatment was significantly lower compared with whites (61.2% v 70.4%; P < .0001). After adjustment for age, sex, median income, cancer stage, tumor size, and comorbidity index, blacks were less likely to undergo nephrectomy treatment compared with whites (risk ratio = 0.93; 95% CI, 0.90 to 0.96). Overall survival was worse for blacks than whites even after adjustment for demographic and cancer prognostic factors (hazard ratio [HR] = 1.16; 95% CI, 1.07 to 1.25); however, additional adjustment for comorbidity index and nephrectomy treatment reduced the disparity substantially (HR = 1.00; 95% CI, 0.93 to 1.09).This study indicates that the lower survival rate among blacks compared with whites with renal cell cancer can be explained largely by the increased number of comorbid health conditions and the lower rate of surgical treatment among black patients.
Differential proteome analysis of human gliomas stratified for loss of heterozygosity on chromosomal arms 1p and 19q
Authors: M. Grzendowski, M. Wolter, M. J. Riemenschneider, C. B. Knobbe, U. Schlegel, H. E. Meyer, G. Reifenberger, K. Stuhler
Journal: Neuro-Oncology (2010)

Combined deletion of chromosomal arms 1p and 19q is an independent prognostic marker in patients with oligodendroglial brain tumors, including oligodendrogliomas and oligoastrocytomas.However, the relevant genes in these chromosome arms and the molecular mechanisms underlying the prognostic significance of 1p/19q deletion are yet unknown.We used two-dimensional difference gel electrophoresis followed by mass spectrometry to perform a proteome-wide profiling of low-grade oligoastrocytomas stratified for the presence or absence of 1p/19q deletions.Thereby, we identified 22 different proteins showing differential expression in tumors with or without combined deletions of 1p and 19q.Four of the differentially expressed proteins, which are vimentin, villin 2 (ezrin), annexin A1, and glial fibrillary acidic protein, were selected for further analysis.Lower relative expression levels of these proteins in 1p/19q-deleted gliomas were confirmed at the protein level by Western blot analysis and immunohistochemistry. Furthermore, sequencing of sodium bisulfitetreated tumor DNA revealed more frequent methylation of 5 0 -CpG islands associated with the VIM and VIL2 genes in 1p/19q-deleted gliomas when compared with gliomas without these deletions.In summary, we confirm proteome-wide profiling as a powerful means to identify candidate biomarkers in gliomas.In addition, our data support the hypothesis that 1p/19q-deleted gliomas frequently show epigenetic down-regulation of multiple genes due to aberrant methylation of the 5 0 -CpG islands.
The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes
Authors: Fan Mou, Maria Praskova, Fan Xia, Denille Van Buren, Hanno Hock, Joseph Avruch, Dawang Zhou
Journal: The Journal of Experimental Medicine (2012)

The Mst1 kinase is an important regulator of murine T cell adhesion, migration, proliferation, and apoptosis. In this study, we analyze mice lacking both Mst1 and Mst2 in hematopoietic cells. Compared with wild-type mice, these double knockout (DKO) mice exhibit a severe reduction in the number of mature T cells in the circulation and in secondary lymphoid organs (SLOs). CD4+CD8− and CD4−CD8+ single-positive (SP) thymocytes in DKO mice resemble mature T cells of wild-type mice but undergo excessive apoptosis, and their egress from the thymus is reduced by &amp;gt;90%. Even when placed directly in the circulation, DKO SP thymocytes failed to enter SLOs. In SP thymocytes, deficiency of Mst1 and Mst2 abolished sphingosine-1 phosphate– and CCL21-induced Mob1 phosphorylation, Rac1 and RhoA GTP charging, and subsequent cell migration. When phosphorylated by Mst1 or Mst2, Mob1 binds and activates the Rac1 guanyl nucleotide exchanger Dock8, which is abundant in the thymus. Thus, the Mst1 and Mst2 kinases control Rho GTPase activation and the migratory responses of SP thymocytes.
Abstract B58: Neurofibromin: A required GAP in lens development
Authors: Christian J. Carbe, Xin Zhang
Journal: Cancer Research (2009)

Abstract Human neurofibromatosis 1 (NF1) is an autosomal dominant genetic disease characterized by multiple discrete dermal neurofibromas as well as optic and other central nervous system gliomas. NF1 patients have a high incidence of additional clinical symptoms including cafe-au-lait spots, hamartomas in the iris (Lisch nodules), macrocephaly, short stature, seizures, and learning disabilities. Neurofibromin, the protein product of the Nf1 gene has been shown to function as a Ras-GTPase activating protein (GAP), thus making it a tumor suppressor protein. Neurofibromin may also regulate adenyl cyclase activity and intracellular cyclic-AMP generation. Here, we show that neurofibromin, as a functional GAP protein, is required for normal murine lens induction. Utilizing a previously developed strain of Nf1-deficient mice, we demonstrate that Nf1−/− embryos exhibit severe lens hypoplasia, and in some cases, anophthalmia. By analyzing RNA (Ras target gene expression) as well as target protein expression patterns (Phopho-ERK), we demonstrate that MAPK signaling is indeed upregulated in the lens region of the developing Nf1−/− embryo at E9, but down regulated after E10. Interestingly we observe a simultaneous down-regulation of transcription factors Pax6, and Sox2, both necessary for normal lens development after E10, which, is the same time we begin to observe poor or absent lens induction. However, the smaller deformed lenses that do form in the Nf1 mutants still express key lens marker proteins (alpha-A crystalline, Prox1), indicating that lens cell differentiation appears to occur normally after lens induction. Cell proliferation studies (BrdU immunohistochemistry) at both E9 and E10 revealed E9 Nf1−/− lens cell proliferation to be normal, however, significantly decreased at E10. In addition, TUNNEL staining performed at both E9 and E10 indicate normal apoptosis in the developing Nf1−/− lens. To test our hypothesis that increased MAPK signaling is the mechanistic cause of the hypoplastic lens, we initiated rescue experiments by injecting E10-pregnant females with MEK inhibitor UO126 and then analyzed the lenses of E12-harvested embryos. Our results do show that attenuation of the MAPK pathway does indeed rescue the mutant lens phenotype, thus confirming our assertion that neurofibromin is an essential GAP protein required for normal lens development. Citation Information: Cancer Res 2009;69(23 Suppl):B58.
IκB kinase β–induced phosphorylation of CARMA1 contributes to CARMA1–Bcl10–MALT1 complex formation in B cells
Authors: Hisaaki Shinohara, Shiori Maeda, Hiroshi Watarai, Tomohiro Kurosaki
Journal: The Journal of Experimental Medicine (2007)

Protein kinase C (PKC) beta has been reported (Shinohara, H., T. Yasuda, Y. Aiba, H. Sanjo, M. Hamadate, H. Watarai, H. Sakurai, and T. Kurosaki. 2005. J. Exp. Med. 202:1423-1431; Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E. Moreno-Garcia, Y.L. Ovechkina, and D.J. Rawlings. 2005. Immunity. 23:561-574) to play a crucial role in B cell receptor (BCR)-mediated IkappaB kinase (IKK) activation through phosphorylation of caspase recruitment domain 11, Bimp3 (CARMA1). However, it remains unclear whether this PKCbeta-mediated phosphorylation accounts fully for the activation status of CARMA1, because involvement of other kinases, such as phosphoinositide 3-kinase-dependent kinase 1, has also been suggested. We show that PKCbeta mediates phosphorylation of CARMA1 on Ser668, which in turn is essential for BCR-mediated CARMA1-Bcl10-mucosal-associated lymphoid tissue 1 (MALT1) association and subsequent IKK activation. Our analyses also demonstrate that the downstream kinase IKKbeta contributes to facilitating formation of the complex CARMA1-Bcl10-MALT1 by mediating phosphorylation of CARMA1. Hence, our data suggest that PKCbeta is crucial for initial activation of IKK. The activated IKKbeta does not merely function as an effector enzyme but also modifies the upstream signaling complex through a feedback mechanism, thereby optimizing the strength and duration of the nuclear factor kappaB signal.
Effects of positive pressure on both femoral venous and arterial blood velocities and the cutaneous microcirculation of the forefoot
Authors: B Fromy
Journal: Cardiovascular Research (1997)

The balance between the apparent beneficial effect and the risk of arterial ischaemia resulting from an external uniform compression is unclear. The purpose of this study was to determine the effects of a positive uniform compression on the lower limb circulation until a critical threshold was reached.We used Doppler ultrasound to measure femoral venous and arterial blood velocities. The effects of positive pressure on cutaneous microcirculation were evaluated by laser Doppler flux (LDF), transcutaneous oxygen pressure (tcpO2) and transcutaneous carbon dioxide pressure (tcpCO2) on the forefoot of 17 healthy subjects.The results are expressed as median [lowest observed value-highest observed value]. Whereas the arterial femoral velocity (A.F.V.) decreased from 0.21 [0.08-0.36] to 0.17 [0.08-0.28] m s-1 for an external pressure as low as 10 mmHg (p < 0.001), the venous femoral velocity (V.F.V.) decreased from 0.13 [0.06-0.40] to 0.09 [0.05-0.34] m s-1 at 20 mmHg (p < 0.001). An increase of tcpCO2 from 39.8 [29.9-53.7] to 40.2 [30.0-55.5] mmHg (p < 0.05) and a decrease of LDF from 8.7 [3.1-25.9] to 5.5 [2.3-21.1] A.U. (p < 0.001) occurred at 10 mmHg. However, tcpO2 decreased only from 76.7 [40.2-91.2] to 64.6 [18.9-85.2] mmHg when the splint pressure reached 60 mmHg (p < 0.05). The observed parameters (LDF, tcpO2, V.F.V. and A.F.V.) decreased further (except for tcpCO2 which increased) up to the end of the study as the applied pressure was increased.Positive pressure on the full leg provided no significant beneficial effect on femoral venous blood velocity. Whereas we showed that for an external uniform pressure as low as 10 mmHg, significant impairments in both arterial inflow of the lower limb and microcirculation of the forefoot appeared in recumbent healthy young subjects.
Circadian Rhythms and Metabolic Syndrome
Authors: Eleonore Maury, Kathryn Moynihan Ramsey, Joseph Bass
Journal: Circulation Research (2010)

Abstract : The incidence of the metabolic syndrome represents a spectrum of disorders that continue to increase across the industrialized world. Both genetic and environmental factors contribute to metabolic syndrome and recent evidence has emerged to suggest that alterations in circadian systems and sleep participate in the pathogenesis of the disease. In this review, we highlight studies at the intersection of clinical medicine and experimental genetics that pinpoint how perturbations of the internal clock system, and sleep, constitute risk factors for disorders including obesity, diabetes mellitus, cardiovascular disease, thrombosis and even inflammation. An exciting aspect of the field has been the integration of behavioral and physiological approaches, and the emerging insight into both neural and peripheral tissues in disease pathogenesis. Consideration of the cell and molecular links between disorders of circadian rhythms and sleep with metabolic syndrome has begun to open new opportunities for mechanism-based therapeutics.
Diabetes conveys a higher risk of gastric cancer mortality despite an age-standardised decreasing trend in the general population in Taiwan
Authors: C.-H. Tseng
Journal: Gut (2010)

<h3>Background</h3> The association between diabetes and gastric cancer has been rarely studied. <h3>Objective</h3> To investigate gastric cancer mortality trends, the mortality rate ratios between patients with diabetes and the general population, and the risk factors for gastric cancer mortality in diabetic patients. <h3>Methods</h3> In the Taiwanese general population from 1995 to 2006, age-standardised trends of gastric cancer mortality were evaluated, followed by calculation of age–sex-specific mortality rates. A total of 113 347 men with diabetes and 131 573 women with diabetes, aged ≥25 years and recruited in 1995–1998, were followed to 2006 for gastric cancer mortality. Age–sex-specific mortality rate ratios for diabetic patients versus the general population were calculated. Cox9s regression was used to evaluate the risk factors among diabetic patients. <h3>Results</h3> A decreasing trend of age-standardised gastric cancer mortality in the general population (p&lt;0.0001) was observed from 1995 to 2006 for both sexes. A total of 627 diabetic men and 422 diabetic women died of gastric cancer, with a calculated mortality rate of 72.8 and 40.0 per 100 000 person-years, respectively. Mortality rate ratios showed a significantly higher risk in diabetic patients with a magnitude most remarkable at the youngest age: 1.52 (1.31–1.77), 1.58 (1.40–1.78) and 4.49 (3.93–5.12) for ≥75, 65–74 and 25–64 years old, respectively, for men; and 1.58 (1.32–1.90), 1.95 (1.67–2.27) and 3.65 (3.11–4.28), respectively, for women. In the diabetic patients, age and male sex were associated with gastric cancer mortality, but diabetes type, insulin use, and smoking were not. Body mass index and area of residence did not show consistent association. Diabetes duration was significantly predictive when those who died of gastric cancer within 5 years of diabetes diagnosis were excluded from analysis. <h3>Conclusions</h3> Despite a decreasing age-standardised mortality trend in the general population, diabetic patients have a higher risk of gastric cancer mortality and this was most remarkable in the youngest age group of 25–64 years.
Increased risk of tumor seeding after percutaneous radiofrequency ablation for single hepatocellular carcinoma
Authors: Josep M. Llovet, Ramon Vilana, Concepció Brú, Lluís Bianchi, Joan Manuel Salmeron, Loreto Boix, Sergi Ganau, Margarita Sala, Mario Pagès, Carmen Ayuso, Manel Solé, Joan Rodés, Jordi Bruix
Journal: Hepatology (2001)

Radiofrequency (RF) ablation is an alternative to percutaneous ethanol injection (PEI) for single nonsurgical hepatocellular carcinoma (HCC) and is currently used as adjuvant therapy before liver transplantation. This phase II study assesses the treatment–related complications and response rate of RF for the treatment of single HCC ≤5 cm. Percutaneous RF was performed under conscious sedation and ultrasound (US) guidance with an electrical generator connected to a single cooled–tip electrode. Neoplastic cells in peripheral blood (reverse transcription–polymerase chain reaction for alpha fetoprotein [AFP] messenger RNA) were analyzed before and after RF. Treatment response was assessed by spiral computed tomography (CT) at 1 month and every 3 months by US or spiral CT thereafter. Thirty–two patients (20 men; age 67 ± 4 years; 78% hepatitis C virus; 24 Child–Pugh A) with a mean tumor size of 2.8 cm (25 patients ≤3 cm) were treated by RF (1.25 sessions; mean time, 22.1 ± 2 minutes). Adjuvant PEI was performed in 9 cases. Complete response was achieved in 21 patients (65%), being significantly higher for HCC ≤3 cm (76% vs. 29%, P = .03). After a median follow–up of 10 months, 8 patients showed treatment–related morbidity. Four of them (12.5%) showed biopsy–proven needle–track seeding detected between 4 to 18 months. Neoplastic seeding was related to subcapsular location ( P = .009), poor differentiation degree ( P = .02), and baseline AFP levels ( P = .02). Thus, RF ablation with cooled–tip needle for HCC is associated with a high risk of neoplastic seeding. Iatrogenic dissemination was related to subcapsular location or an invasive tumoral pattern, and has to be considered when selecting curative treatments for HCC or adjuvant therapies before liver transplantation.
Nitric oxide levels in exhaled air and inducible nitric oxide synthase immunolocalization in pulmonary sarcoidosis
Authors: Y.P. Moodley, R. Chetty, U.g Lalloo
Journal: European Respiratory Journal (1999)

The dust content of grapes in New York vineyards was found to range from 2 to 47 ppm and averaged 19 ppm for the three-year period of this study. When the grapes were washed on the vine with sprays of water from conventional vineyard sprayers, the dust content could be reduced by approximately 30%. The effectiveness of the washing was determined by the density of the foliage. The foliage of grape vines grown on Umbrella trellises was denser and more difficut to penetrate than that of vines grown on the Geneva Double Curtain, where the grape clusters were more exposed to the water sprays. Hand-harvested grapes are washed at the factory, but their dirt content does not appear to be significantly lower than that of fruit on the vine, owing to contamination during shipping. Under New York State conditions, if would appear possible to obtain as clean grapes by mechanical harvesting without washing as is now possible by factory washing of hand harvested fruit.
Effects of chronic progressive myocardial hypertrophy on indexes of cardiac autonomic innervation.
Authors: K Lindpaintner, D D Lund, P G Schmid
Journal: Circulation Research (1987)

The development of cardiac hypertrophy is associated with marked changes in cardiac autonomic innervation. Significant and sustained reductions of myocardial catecholamine stores and activities of tyrosine hydroxylase and dopamine beta-hydroxylase have been reported in models of acutely induced ventricular hypertrophy. Conversely, activity of choline acetyltransferase, a marker of parasympathetic nervous function, shows transient increases during the development of acute right ventricular hypertrophy. The potential physiological importance of these changes prompted us to examine a clinically more relevant model of slowly progressive ventricular hypertrophy. Application of a loose band around the pulmonary artery of weanling guinea pigs resulted in a growth-related progressive right ventricular pressure overload. Right ventricular weight-to-body-weight ratio was increased significantly and progressively at 9 and 18 weeks in banded animals (0.92 +/- 0.05 and 1.31 +/- 0.11 mg/g, respectively, p less than 0.01) compared with sham-operated controls (0.55 +/- 0.02 and 0.59 +/- 0.01 mg/g, respectively) but showed no further gain at 27 weeks (1.41 +/- 0.10 mg/g). Activities of tyrosine hydroxylase and dopamine beta-hydroxylase remained unchanged in all experiment groups, while right ventricular contents of norepinephrine in banded animals at 18 and 27 weeks exhibited sustained and progressive increases (2.45 +/- 0.11 and 3.40 +/- 0.19 micrograms/right ventricle, respectively) over controls (1.80 +/- 0.13 and 2.40 +/- 0.22 micrograms/right ventricle, respectively, p less than 0.01). The activity of choline acetyltransferase was markedly elevated in banded animals at 18 weeks (32.6 +/- 2.7 nmol/hr/right ventricle) but returned to baseline by 27 weeks (22.8 +/- 1.4 nmol/hr/right ventricle).(ABSTRACT TRUNCATED AT 250 WORDS)
Eight Weeks of Esomeprazole Therapy Reduces Symptom Relapse, Compared With 4 Weeks, in Patients With Los Angeles Grade A or B Erosive Esophagitis
Authors: Ping-I Hsu, Ching-Liang Lu, Deng-Chyang Wu, Chao-Hung Kuo, Sung-Shuo Kao, Chun-Chao Chang, Wei-Chen Tai, Kwok-Hung Lai, Wen-Chih Chen, Huay-Min Wang, Jin-Shiung Cheng, Tzung-Jiun Tsai, Seng-Kee Chuah
Journal: Clinical Gastroenterology and Hepatology (2014)
RE: Racial Differences in Mortality Among Medicare Recipients After Treatment for Localized Prostate Cancer
Authors: C. T. Lee
Journal: JNCI Journal of the National Cancer Institute (2004)

The recent article by Godley et al. (1) raises important concerns for those who manage localized prostate cancer.The authors found that African Americans who underwent surgery, radiation, or non-aggressive therapy for localized prostate cancer had a median overall survival that was 1.8, 0.7, and 1.0 years less than that of Caucasians treated with the same respective modality.Moreover, a significant disadvantage in overall survival was seen in African American surgical patients after adjusting for age, comorbidity score, stage, cancer grade, SEER 1 site, and race-specific census tract level measures of education and income.Although the multivariable analysis was limited by the exclusion of serum prostate-specific antigen (PSA)
2-Agonists block tussive responses in guinea pigs via an atypical cAMP-dependent pathway
Authors: V. C. Freund-Michel, M. A. Birrell, M. A. Giembycz, D. J. Hele, S. Haj-Yahia, M. G. Belvisi
Journal: European Respiratory Journal (2009)

β 2 -Adrenoceptor agonists are the most effective bronchodilators currently available, and are used for symptom management in asthmatics. However, whether β 2 -agonists are also antitussive is controversial. Identifying an antitussive role for β 2 -agonists and dissecting the possible mechanism of action may help to explain the inconsistencies in the clinical literature and lead to the development of novel therapeutic agents. The aim of the present study was to determine whether or not β 2 -agonists attenuate the tussive response in guinea pig and human models, and, if so, to identify the mechanism(s) involved. Depolarisation of vagal sensory nerves (human and guinea pig) was assessed as an indicator of sensory nerve activity. Cough was measured in a conscious guinea pig model. A β 2 -agonist, terbutaline, dose-dependently inhibited the cough response to tussive agents in conscious guinea pigs. Terbutaline and another β 2 -agonist, fenoterol, blocked sensory nerve activation in vitro . Using these mechanistic models, it was established that β 2 -agonists suppress the tussive response via a nonclassical cyclic adenosine monosphosphate-dependent pathway that involves the activation of protein kinase G and, subsequently, the opening of large-conductance calcium-activated potassium channels. In conclusion, β 2 -adrenoceptor agonists are antitussive, and this property occurs due to a direct inhibition of sensory nerve activation. These findings may help to explain the confusion that exists in the clinical literature, and could be exploited to identify novel therapies for the treatment of cough, which is a significant unmet medical need.
Civatte bodies and the actively dividing epithelial cells in oral lichen planus
Authors: N.G. EL-LABBAN, IVOR R.H. KRAMER
Journal: British Journal of Dermatology (2006)

The relationship between Civatte bodies and epithelial cells in mitosis was investigated in lichen planus lesions of the oral mucosa. The nuclear material in Civatte bodies was often very similar to that in normal dividing basal epithelial cells. In addition, cells were found with clearly identifiable chromosomes, but with cytoplasmic changes of Civatte bodies. These results suggest that Civatte bodies are probably the outcome of degenerative changes affecting epithelial cells in various stages of mitosis.