tbuckley/cabot-search huggingface dataset:
Spectral oscillations of RR intervals in sleep apnoea/hypopnoea syndrome patients
Authors: K. Dingli, T. Assimakopoulos, P.K. Wraith, I. Fietze, C. Witt, N.J. Douglas
Journal: European Respiratory Journal (2003)

A recent study has shown that daytime heart rate variability is reduced in obstructive sleep apnoea/hypopnoea syndrome (OSAHS) patients. In the present study, the hypothesis was that sympathovagal balance around apnoeas/hypopnoeas and nocturnal autonomic activity are altered in OSAHS patients. Frequency- and time-domain analyses of RR intervals were performed to monitor sympathovagal activity noninvasively. Fourteen untreated OSAHS patients and seven healthy subjects underwent overnight polysomnography. Low (LF) and total (TF) frequency power increased 2 min around the end of apnoeas/hypopnoeas (LF 229±38 ms 2 , TF 345±45 ms 2 ) compared with undisturbed sleep (LF 106±18 ms 2 , TF 203±23 ms 2 ). The increase in high frequency (HF) power was not significant. LF increase was proportionally higher than the HF increase (normalised LF (LFn) 67±1 units, normalised HF (HFn) 33±1 units) compared with undisturbed sleep (LFn 52±2 units, HFn 48±2 units). RR duration did not change around apnoeas/hypopnoeas (RR 904±28 ms). The LF and TF power increase was greater around arousal-inducing (LF 260±45 ms 2 , TF 390±65 ms 2 ) compared with self-terminating (LF 161±31 ms 2 , TF 249±40 ms 2 ) apnoeas/hypopnoeas; the LF and LFn increases were significant in both groups compared with undisturbed sleep and HF power differences were nonsignificant. RR intervals were longer around self-terminating apnoeas/hypopnoeas (RR 914±29 ms); the differences were not significant compared with undisturbed sleep. RR interval spectral power was not influenced by the event type. RR duration decreased (912±28 ms) and LF, HF and TF power increased (LF 111±16 ms 2 , HF 62±6 ms 2 , TF 173±21 ms 2 ) across patients, compared with healthy controls (RR 1138±91 ms, LF 57±3 ms 2 , HF 35±3 ms 2 , TF 91±6 ms 2 ). LFn and HFn did not change significantly. Sympathetic activity increases around apnoeas/hypopnoeas. The recurrent nocturnal fluctuations of sympathovagal balance and the overall increase of nocturnal autonomic activity may be of importance in the development of cardiovascular disease in sleep apnoea patients.
Absence of E-Cadherin Expression Distinguishes Noncohesive from Cohesive Pancreatic Cancer
Authors: Jordan M. Winter, Angela H. Ting, Felip Vilardell, Eike Gallmeier, Steve B. Baylin, Ralph H. Hruban, Scott E. Kern, Christine A. Iacobuzio-Donahue
Journal: Clinical Cancer Research (2008)

Abstract Purpose: The role of E-cadherin in carcinogenesis is of great interest, but few studies have examined its relevance to pancreatic carcinoma. Experimental Design: We evaluated E-cadherin protein expression by immunohistochemistry in pancreatobiliary cancers having a noncohesive histologic phenotype (21 undifferentiated adenocarcinomas and 7 signet ring carcinomas), comparing the results with pancreatic cancers having a cohesive phenotype (25 moderately differentiated and 14 poorly differentiated adenocarcinomas). Results: Twenty of 21 undifferentiated cancers had complete absence of E-cadherin expression, as did two signet ring carcinomas. In contrast, cohesive cancers (n = 39) had E-cadherin labeling at the plasma membrane (P &amp;lt; 0.001). Subsets of cancers were also evaluated for β-catenin expression. All of the cohesive lesions (n = 28) showed a membranous β-catenin expression pattern, whereas noncohesive foci (n = 7) were characterized by either cytoplasmic labeling or complete absence of β-catenin protein expression, suggestive of a deficient zonula adherens in noncohesive cancers. E-cadherin promoter hypermethylation was observed in an undifferentiated pancreatic cancer cell line, MiaPaCa-2, whereas two pancreatic cancer cell lines derived from differentiated lesions lacked any evidence of E-cadherin promoter methylation. No pattern of E-cadherin promoter methylation could be determined in three primary cancers having mixed histologic patterns (contained both cohesive and noncohesive foci). No somatic mutations in E-cadherin were identified in noncohesive pancreatic cancers having inactivated E-cadherin. Conclusions: Noncohesive pancreatic cancers were characterized by the loss of E-cadherin protein expression. Promoter hypermethylation is a possible mechanism of E-cadherin gene silencing in a subset of these cancers.
The expression status of CD133 is associated with the pattern and timing of primary glioblastoma recurrence
Authors: Ichiyo Shibahara, Yukihiko Sonoda, Ryuta Saito, Masayuki Kanamori, Yoji Yamashita, Toshihiro Kumabe, Mika Watanabe, Hiroyoshi Suzuki, Takashi Watanabe, Chikashi Ishioka, Teiji Tominaga
Journal: Neuro-Oncology (2013)

Glioblastoma carries a poor prognosis primarily because of its high rate of recurrence. The ability to predict the recurrence pattern and timing would be highly useful for determining effective treatment strategies. We examined the correlation between prognostic factors and the pattern of recurrence in patients with primary glioblastoma. In particular, we examined whether there was a correlation between the expression of CD133 and glioblastoma recurrence. We retrospectively analyzed 112 patients with primary glioblastoma. The timing and pattern (local or distant) of the initial recurrence were obtained from medical records. To identify factors predictive of recurrence, we examined CD133 expression by Western blots and immunohistochemistry, clinical (age, sex, KPS, Ki67 labeling index, surgery, ventricular entry) and genetic (IDH1, 7p, 9p, 10q, MGMT) factors. Of the 112 patients, 99 suffered recurrence. The first recurrence was local in 77 patients and distant in 22 patients. Among the factors to predict the pattern of recurrence, CD133 expression was significantly higher in distant than in local recurrence. Of the factors to predict the timing of recurrence, high CD133 expression was associated with shorter time to distant recurrence in both univariate and multivariate analyses (P = .0011 and P = .038, respectively). The expression of CD133 may be a predictor of the pattern and timing of recurrence of primary glioblastoma.
Predicting Cancer Progression in Patients With Stage T1 Bladder Carcinoma
Authors: Liang Cheng, Roxann M. Neumann, Amy L. Weaver, Bruce E. Spotts, David G. Bostwick
Journal: Journal of Clinical Oncology (1999)

A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach.The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer.The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P =.037). The 5-year progression-free survival rate for patients with depth of invasion of >/= 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P =.009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression.The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.
Altered sensitivity to reward in children with ADHD: Dopamine timing is off
Authors: Jeffery R. Wickens, E. Gail Tripp
Journal: Behavioral and Brain Sciences (2005)

despite general agreement that altered reward sensitivity is involved in attention-deficit/hyperactivity disorder (adhd), a wide range of different alterations has been proposed. we cite work showing abnormal sensitivity to delay of reward, together with abnormal sensitivity to individual instances of reward. we argue that at the cellular level these behavioural characteristics might indicate that dopamine timing is off in children with adhd.
Activation of the Succinate Receptor GPR91 in Macula Densa Cells Causes Renin Release
Authors: Sarah Laurin Vargas, Ildikó Toma, Jung Julie Kang, Elliott James Meer, János Peti-Peterdi
Journal: Journal of the American Society of Nephrology (2009)

Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) are salt sensors and generate paracrine signals that control renal blood flow, glomerular filtration, and release of the prohypertensive hormone renin. We hypothesized that the recently identified succinate receptor GPR91 is present in MD cells and regulates renin release. Using immunohistochemistry, we identified GPR91 in the apical plasma membrane of MD cells. Treatment of MD cells with succinate activated mitogen-activated protein kinases (MAPKs; p38 and extracellular signal-regulated kinases 1/2) and cyclooxygenase 2 (COX-2) and induced the synthesis and release of prostaglandin E(2), a potent vasodilator and classic paracrine mediator of renin release. Using microperfused JGA and real-time confocal fluorescence imaging of quinacrine-labeled renin granules, we detected significant renin release in response to tubular succinate (EC(50) 350 microM). Genetic deletion of GPR91 (GPR91(-/-) mice) or pharmacologic inhibition of MAPK or COX-2 blocked succinate-induced renin release. Streptozotocin-induced diabetes caused GPR91-dependent upregulation of renal cortical phospho-p38, extracellular signal-regulated kinases 1/2, COX-2, and renin content. Salt depletion for 1 wk increased plasma renin activity seven-fold in wild-type mice but only 3.4-fold in GPR91(-/-) mice. In summary, MD cells can sense alterations in local tissue metabolism via accumulation of tubular succinate and GPR91 signaling, which involves the activation of MAPKs, COX-2, and the release of prostaglandin E(2). This mechanism may be integral in the regulation of renin release and activation of the renin-angiotensin system in health and disease.
Prehospital-Initiated vs Hospital-Initiated Thrombolytic Therapy
Authors: W D Weaver, M Cerqueira, A P Hallstrom, P E Litwin, J S Martin, P J Kudenchuk, M Eisenberg
Journal: JAMA (1993)

To determine the effect of prehospital-initiated vs hospital-initiated treatment of myocardial infarction on clinical outcome.Randomized, controlled clinical trial.Multicenter study involving 19 hospitals and all paramedic systems in the Seattle, Wash, metropolitan area.A total of 360 patients with symptoms for 6 hours or less, no risk factors for serious bleeding, and ST-segment elevation were selected by paramedics and a remote physician for inclusion into the trial. They represented 4% of patients with chest pain who were screened and 21% of those with acute infarction.Patients were allocated to have aspirin and alteplase treatment initiated before or after hospital arrival. Intravenous sodium heparin was administered to both groups in the hospital.The primary endpoint was a ranked composite score (combining death, stroke, serious bleeding, and infarct size). The relation between time to treatment and outcome (composite score, infarct size, ejection fraction, and mortality) was also assessed.Initiating treatment before hospital arrival decreased the interval from symptom onset to treatment from 110 to 77 minutes (P < .001). Although more patients whose therapy was initiated before hospital arrival had resolution of pain by admission (23% vs 7%; P < .001), there were no significant differences in the composite score (P = .64), mortality (5.7% vs 8.1%), ejection fraction (53% vs 54%), or infarct size (6.1% vs 6.5%). A secondary analysis of time to treatment and outcome showed that treatment initiated within 70 minutes of symptom onset was associated with better outcome (composite score, P = .009; mortality, 1.2% vs 8.7%, P = .04; infarct size, 4.9% vs 11.2%, P < .001; and ejection fraction, 53% vs 49%, P = .03) than later treatment. Identification of patients eligible for thrombolysis by paramedics reduced the hospital treatment time from 60 minutes (for patients not in the study) to 20 minutes (for study patients allocated to begin treatment in the hospital).There was no improvement in outcome associated with initiating treatment before hospital arrival; however, treatment within 70 minutes of symptom onset--whether in the hospital or in the field--minimized the infarct process and its complications.
Cyclooxygenase-2 Inhibition Suppresses αvβ6 Integrin–Dependent Oral Squamous Carcinoma Invasion
Authors: Maria L. Nystrom, Diana McCulloch, Paul H. Weinreb, Shelia M. Violette, Paul M. Speight, John F. Marshall, Ian R. Hart, Gareth J. Thomas
Journal: Cancer Research (2006)

Abstract Worldwide oral squamous cell carcinoma (OSCC) represents about 5.5% of all malignancies, with ∼30,000 new cases each year in the United States. The integrin αvβ6 and the enzyme cyclooxygenase-2 (COX-2) are implicated in OSCC progression and have been suggested as possible therapeutic targets. Each protein also is reported to identify dysplasias at high risk of malignant transformation, and current clinical trials are testing the efficacy of nonsteroidal anti-inflammatory drugs (NSAID) at preventing OSCC development. Given the probable increased expression of αvβ6 and COX-2 in OSCC and the inhibition of several integrins by NSAIDs, we investigated whether NSAIDs affected αvβ6-dependent cell functions. We found that expression of both αvβ6 and COX-2 was significantly higher in OSCC compared with oral epithelial dysplasias. Neither protein preferentially identified those dysplastic lesions that became malignant. Using OSCC cell lines, modified to express varying levels of αvβ6, we assessed the effect of COX-2 inhibition on cell invasion. We found that the COX-2 inhibitor NS398 inhibited specifically αvβ6-dependent, but not αvβ6-independent, OSCC invasion in vitro and in vivo, and this effect was modulated through prostaglandin E2 (PGE2)–dependent activation of Rac-1. Transient expression of constitutively active Rac-1, or addition of the COX-2 metabolite PGE2, prevented the anti-invasive effect of NS398. Conversely, RNA interference down-regulation of Rac-1 inhibited αvβ6-dependent invasion. These findings suggest that COX-2 and αvβ6 interact in promoting OSCC invasion. This is a novel mechanism that, given the ubiquity of αvβ6 expression by head and neck cancers, raises the possibility that NSAIDs could protect against OSCC invasion. (Cancer Res 2006; 66(22): 10833-42)
Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial
Authors: Nathan H Fowler, R Eric Davis, Seema Rawal, Loretta Nastoupil, Fredrick B Hagemeister, Peter McLaughlin, Larry W Kwak, Jorge E Romaguera, Michelle A Fanale, Luis E Fayad, Jason R Westin, Jatin Shah, Robert Z Orlowski, Michael Wang, Francesco Turturro, Yasuhiro Oki, Linda C Claret, Lei Feng, Veerabhadran Baladandayuthapani, Tariq Muzzafar, Kenneth Y Tsai, Felipe Samaniego, Sattva S Neelapu
Journal: The Lancet Oncology (2014)
Interferon-α therapy in patients dually infected with hepatitis C virus and GB virus C/hepatitis G virus — virological response of HGV and pretreatment HGV viremia level
Authors: Etsuro Orito, Masashi Mizokami, Kiyomi Yasuda, Kanji Sugihara, Makoto Nakamura, Motokazu Mukaide, Ken-Ichi Ohba, Tatsunori Nakano, Takanobu Kato, Yutaka Kondo, Takashi Kumada, Ryuzo Ueda, Shiro Iino
Journal: Journal of Hepatology (1997)
Evolving Dual Targeting of a Prokaryotic Protein in Yeast
Authors: Efrat Burak, Ohad Yogev, Shimon Sheffer, Ora Schueler-Furman, Ophry Pines
Journal: Molecular Biology and Evolution (2013)

Dual targeting is an important and abundant phenomenon. Indeed, we estimate that more than a third of the yeast mitochondrial proteome is dual localized. The enzyme fumarase is a highly conserved protein in all organisms with respect to its sequence, structure, and enzymatic activity. In eukaryotes, it is dual localized to the cytosol and mitochondria. In Saccharomyces cerevisiae, the dual localization of fumarase is achieved by the reverse translocation mechanism; all fumarase molecules harbor a mitochondrial targeting sequence (MTS), are targeted to mitochondria, begin their translocation, and are processed by mitochondrial processing peptidase in the matrix. A subset of these processed fumarase molecules in transit is then fully imported into the matrix, whereas the majority moves back into the cytosol by reverse translocation. The proposed driving force for fumarase distribution is protein folding during import. Here, we asked how reverse translocation could have evolved on a prokaryotic protein that had already acquired expression from the nuclear genome and a targeting sequence. To address this question, we used, as a model, the Escherichia coli FumC Class II fumarase, which is homologous to eukaryotic fumarases (∼58% identity and ∼74% similarity to the yeast Fum1). Starting with an exclusively mitochondrial targeted FumC (attached to a strong MTS), we show that two randomly acquired mutations within the prokaryotic FumC sequence are sufficient to cause substantial dual targeting by reverse translocation. In fact, the unmutated MTS-FumC also has some ability to be dual targeted but only at low temperatures. Our results suggest that in this case, evolution of dual targeting by reverse translocation is based on naturally occurring and fortuitously conserved features of fumarase folding.
Potent Modulation of Intestinal Tumorigenesis in <i>Apcmin/+</i> Mice by the Polyamine Catabolic Enzyme Spermidine/Spermine <i>N</i>1-acetyltransferase
Authors: Jody M. Tucker, John T. Murphy, Nicholas Kisiel, Paula Diegelman, Karen W. Barbour, Celestia Davis, Moussumi Medda, Leena Alhonen, Juhani Jänne, Debora L. Kramer, Carl W. Porter, Franklin G. Berger
Journal: Cancer Research (2005)

Abstract Intracellular polyamine pools are homeostatically maintained by processes involving biosynthesis, catabolism, and transport. Although most polyamine-based anticancer strategies target biosynthesis, we recently showed that activation of polyamine catabolism at the level of spermidine/spermine N1-acetyltransferase-1 (SSAT) suppresses tumor outgrowth in a mouse prostate cancer model. Herein, we examined the effects of differential SSAT expression on intestinal tumorigenesis in the ApcMin/+ (MIN) mouse. When MIN mice were crossed with SSAT-overproducing transgenic mice, they developed 3- and 6-fold more adenomas in the small intestine and colon, respectively, than normal MIN mice. Despite accumulation of the SSAT product, N1-acetylspermidine, spermidine and spermine pools were only slightly decreased due to a huge compensatory increase in polyamine biosynthetic enzyme activities that gave rise to enhanced metabolic flux. When MIN mice were crossed with SSAT knock-out mice, they developed 75% fewer adenomas in the small intestine, suggesting that under basal conditions, SSAT contributes significantly to the MIN phenotype. Despite the loss in catabolic capability, tumor spermidine and spermine pools failed to increase significantly due to a compensatory decrease in biosynthetic enzyme activity giving rise to a reduced metabolic flux. Loss of heterozygosity at the Apc locus was observed in tumors from both SSAT-transgenic and -deficient MIN mice, indicating that loss of heterozygosity remained the predominant oncogenic mechanism. Based on these data, we propose a model in which SSAT expression alters flux through the polyamine pathway giving rise to metabolic events that promote tumorigenesis. The finding that deletion of SSAT reduces tumorigenesis suggests that small-molecule inhibition of the enzyme may represent a nontoxic prevention and/or treatment strategy for gastrointestinal cancers.
Abstract 14930: Comparative Outcomes after Cardiac Resynchronization Therapy in Patients with Right Ventricular Pacing versus Native Wide Left Bundle Branch Block
Authors: Bhupendar Tayal, Antonia Delgado-Montero, Akiko Goda, Keiko Ryo, Samir Saba, Niels Risum, Peter Sogaard, John Gorcsan
Journal: Circulation (2014)

Introduction: Current updated clinical guidelines for cardiac resynchronization therapy (CRT) favor as Class I indications patients with native wide QRS width (≤150ms) and left bundle branch block (LBBB). However, the comparative long term outcome in patients who receive CRT who had right ventricular (RV) pacing at baseline is unknown. Hypothesis: We tested the hypothesis that long-term survival after CRT in patients who were upgraded from RV pacing is similar to those with native wide LBBB. Methods: We studied 146 consecutive CRT patients with either native LBBB and QRS duration ≥150ms or who were RV paced at baseline. All were New York Heart Association Class II, III, or ambulatory IV with ejection fraction <35%. There were 76 (52%) with ischemic disease. Outcome events were predefined as death, heart transplantation or LV assist device (LVAD) implantation over 4 years after CRT. Results: Of the 146 CRT patients, 116 (79%) had native LBBB ≥150ms and 30 (21%) were upgraded from RV pacing. Baseline QRS wi...
Growth Suppression of Ovarian Cancer Xenografts in Nude Mice by Vitamin D Analogue EB1089
Authors: Xiaohui Zhang, Feng Jiang, Pengfei Li, Chunrong Li, Qiuping Ma, Santo V. Nicosia, Wenlong Bai
Journal: Clinical Cancer Research (2005)

The poor response of advanced epithelial ovarian cancer to current treatments necessitates the development of alternative therapeutic strategies. Inhibition of cancer growth by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] compounds represents an innovative approach for cancer therapy. The current study evaluated the therapeutic potential of a synthetic 1,25(OH)2D3 analogue EB1089 in the treatment of ovarian cancer.The response of human ovarian cancer cells to 1,25(OH)2D3 and EB1089 were first compared in cell growth, gene transcription, and apoptotic assays. Then, nude mice bearing OVCAR3 tumor xenografts were treated with EB1089 at different dosages, and tumor volumes were monitored. The effect of EB1089 and 1,25(OH)2D3 on the level of serum calcium was also examined. After the treatment, tumors were excised and processed for histologic examination, Ki-67 staining, and tissue terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assays to evaluate the morphologic, proliferative, and apoptotic changes induced by EB1089, respectively.The study shows that EB1089 suppresses the in vitro growth of ovarian cancer cells and transcriptionally activates the GADD45 reporter gene more effectively than 1,25(OH)2D3. Clinically more importantly, EB1089 suppresses the growth of OVCAR3 tumor xenografts in nude mice without inducing hypercalcemia. Ki-67 staining and tissue TUNEL assays showed that both inhibition of cell proliferation and induction of apoptosis contribute to the EB1089-induced tumor suppression in vivo.This study is the first demonstration that ovarian cancer responds positively in vivo to treatment with a 1,25(OH)2D3 compound and thus supports continued development of 1,25(OH)2D3 analogues for possible use as an alternative or complementary therapy for human ovarian cancer.