tbuckley/cabot-search huggingface dataset:
Molecular Evolution of the Endosperm Starch Synthesis Pathway Genes in Rice (Oryza sativa L.) and Its Wild Ancestor, O. rufipogon L.
Authors: G. Yu, K. M. Olsen, B. A. Schaal
Journal: Molecular Biology and Evolution (2010)

The evolution of metabolic pathways is a fundamental but poorly understood aspect of evolutionary change. One approach for understanding the complexity of pathway evolution is to examine the molecular evolution of genes that together comprise an integrated metabolic pathway. The rice endosperm starch biosynthetic pathway is one of the most thoroughly characterized metabolic pathways in plants, and starch is a trait that has evolved in response to strong selection during rice domestication. In this study, we have examined six key genes (AGPL2, AGPS2b, SSIIa, SBEIIb, GBSSI, ISA1) in the rice endosperm starch biosynthesis pathway to investigate the evolution of these genes before and after rice domestication. Genome-wide sequence tagged sites data were used as a neutral reference to overcome the problems of detecting selection in species with complex demographic histories such as rice. Five variety groups of Oryza sativa (aus, indica, tropical japonica, temperate japonica, aromatic) and its wild ancestor (O. rufipogon) were sampled. Our results showed evidence of purifying selection at AGPL2 in O. rufipogon and strong evidence of positive selection at GBSSI in temperate japonica and tropical japonica varieties and at GBSSI and SBEIIb in aromatic varieties. All the other genes showed a pattern consistent with neutral evolution in both cultivated rice and its wild ancestor. These results indicate the important role of positive selection in the evolution of starch genes during rice domestication. We discuss the role of SBEIIb and GBSSI in the evolution of starch quality during rice domestication and the power and limitation of detecting selection using genome-wide data as a neutral reference.
1,1-Bis(3′-Indolyl)-1-(<i>p</i>-Substitutedphenyl)methanes Induce Apoptosis and Inhibit Renal Cell Carcinoma Growth
Authors: Melissa York, Maen Abdelrahim, Sudhakar Chintharlapalli, Salina D. Lucero, Stephen Safe
Journal: Clinical Cancer Research (2007)

Abstract Purpose: 1,1-Bis(3′-indolyl)-1-(p-substitutedphenyl)methanes [methylene-substituted diindolylmethanes (C-DIM)] containing p-trifluoromethyl, p-t-butyl, and p-phenyl substituents activate peroxisome proliferator-activated receptor γ (PPARγ) and inhibit growth of several different cancer cell lines through receptor-dependent and receptor-independent pathways. The purpose of this study is to investigate the anticancer activity of these compounds in renal cell carcinoma. Experimental Design: The anticancer activity of the p-t-butyl–substituted C-DIM compound (DIM-C-pPhtBu) was investigated in ACHN and 786-0 renal cell carcinoma cell lines and in an orthotopic model for renal carcinogenesis using ACHN cells injected directly into the kidney. Results: PPARγ is overexpressed in ACHN cells and barely detectable in 786-0 cells, and treatment with DIM-C-pPhtBu induces proteasome-dependent degradation of cyclin D1 and variable effects on p21 and p27 expression in both cell lines. DIM-C-pPhtBu also induced several common proapoptotic responses in ACHN and 786-0 cells, including increased expression of nonsteroidal anti-inflammatory drug-activated gene-1 and endoplasmic reticulum stress, which activates death receptor 5 and the extrinsic pathway of apoptosis. Activation of these responses was PPARγ independent. In addition, DIM-C-pPhtBu (40 mg/kg/d) also inhibited tumor growth in an orthotopic mouse model for renal carcinogenesis, and this was accompanied by induction of apoptosis in renal tumors treated with DIM-C-pPhtBu but not in tumors treated with the corn oil vehicle (control). Conclusions: DIM-C-pPhtBu and related compounds are cytotoxic to renal cancer cells and activate multiple proapoptotic and growth-inhibitory pathways. The results coupled with in vivo anticancer activity show the potential of DIM-C-pPhtBu and related C-DIMs for clinical treatment of renal adenocarcinoma.
Phase I/II trial of gene therapy with autologous tumor cells modified with tag7/PGRP-S gene in patients with disseminated solid tumors
Authors: V.M. Moiseyenko, A.O. Danilov, I.A. Baldueva, A.B. Danilova, N.V. Tyukavina, S.S. Larin, S.L. Kiselev, R.V. Orlova, V.V. Anisimov, A.I. Semenova, L.A. Shchekina, G.I. Gafton, V.A. Kochnev, A.S. Barchuk, S.V. Kanaev, K.P. Hanson, G.P. Georgiev
Journal: Annals of Oncology (2004)
A Cardiocardiac Sympathovagal Reflex in the Cat
Authors: PETER J. SCHWARTZ, MASSIMO PAGANI, FEDERICO LOMBARDI, ALBERTO MALLIANI, ARTHUR M. BROWN
Journal: Circulation Research (1973)

The reflex changes in single cardiac vagal efferent fibers elicited by excitation of afferent cardiac sympathetic fibers were studied in cats anesthetized with chloralose and urethane. Efferent vagal and sympathetic units were dissected from the end of a cardiac nerve cut at its junction with the right atrium. In some cases, efferent vagal units were dissected from the cervical vagus. Excitation always evoked a clear reduction in the discharge of cardiac vagal units and a clear increase in the discharge of cardiac sympathetic fibers. The effects on cervical vagal efferents were variable. Hence, excitation of afferent cardiac sympathetic fibers could simultaneously elicit inhibition of the vagal outflow to the heart and excitation of the sympathetic outflow. By contrast, stimulation of the cut central end of the contralateral vagus produced the opposite effects. Convergence of afferent fibers in the vagi and the cardiac sympathetic nerves on the same cardiac vagal and cardiac sympathetic postganglionic neurons was demonstrated. Convergence from carotid sinus baroreceptors was also observed.
Relation of Medial Temporal Lobe Volumes to Age and Memory Function in Nondemented Adults With Down’s Syndrome: Implications for the Prodromal Phase of Alzheimer’s Disease
Authors: Jack S. Krasuski, Gene E. Alexander, Barry Horwitz, Stanley I. Rapoport, Mark B. Schapiro
Journal: American Journal of Psychiatry (2002)

In Down's syndrome (trisomy 21), a dementia syndrome occurs that is phenotypically similar to Alzheimer's disease; the initial phase is characterized by memory loss. The authors used an in vivo structural technique in the predementia stage of Alzheimer's disease in adults with Down's syndrome to investigate whether atrophy of medial temporal lobe structures occurs in these subjects and whether volumes of these structures correlate specifically with performance on memory tests.The subjects were 34 nondemented Down's syndrome adults (mean age=41.6 years, 17 women and 17 men) and 33 healthy comparison subjects (mean age=41.3, 15 women and 18 men). By using T(1)-weighted magnetic resonance imaging slices taken perpendicular to the Sylvian fissure, volumes of the hippocampus, amygdala, anterior and posterior parahippocampal gyrus, and temporal pole CSF were measured in both hemispheres. These data were normalized to the total intracranial volume.For Down's syndrome, smaller volumes of the right and left amygdala, hippocampus, and posterior parahippocampal gyrus were significantly associated with greater age; this association was not seen in the anterior parahippocampal gyrus. The amygdala and hippocampus volumes were positively correlated with memory measures. For the comparison group, there was no relationship between volume and age in any region.In the predementia phase of Down's syndrome, significant volume changes in medial temporal lobe structures occur with age and are related to memory. These structures are affected early in Alzheimer's disease in Down's syndrome, and their evaluation may help identify people in the preclinical stages of Alzheimer's disease.
A Functional Element Necessary for Fetal Hemoglobin Silencing
Authors: Vijay G. Sankaran, Jian Xu, Rachel Byron, Harvey A. Greisman, Chris Fisher, David J. Weatherall, Daniel E. Sabath, Mark Groudine, Stuart H. Orkin, Anuja Premawardhena, M.A. Bender
Journal: New England Journal of Medicine (2011)

An improved understanding of the regulation of the fetal hemoglobin genes holds promise for the development of targeted therapeutic approaches for fetal hemoglobin induction in the β-hemoglobinopathies. Although recent studies have uncovered trans-acting factors necessary for this regulation, limited insight has been gained into the cis-regulatory elements involved.
South-Asian Type 2 Diabetic Patients Have Higher Incidence and Faster Progression of Renal Disease Compared With Dutch-European Diabetic Patients
Authors: Prataap K. Chandie Shaw, Fazil Baboe, Leendert A. van Es, J. Carel van der Vijver, Marcel A. van de Ree, Niels de Jonge, Ton J. Rabelink
Journal: Diabetes Care (2006)

Surinamese South-Asian migrants, living in the Netherlands and aged >30 years, have a nearly 40-fold increased age-adjusted risk for end-stage diabetic nephropathy in comparison with their European Dutch counterparts (1). Several studies in the U.K. also showed a higher incidence of end-stage renal failure in South-Asian diabetic patients (2,3,4,5,6).

There is no clear explanation for the increased risk in South-Asian migrants, who originally descend from the Indian subcontinent. An earlier study showed no familial predisposition for renal disease in South-Asian migrants (7). There is a discrepancy between the reported eight-times higher prevalence of diabetes (8) and the 40-fold higher risk of end-stage diabetic nephropathy (1) in this population. This discrepancy could be explained by either a higher incidence of nephropathy in the Asian diabetic patients and/or faster progression to end-stage renal failure.

We performed a cohort study in South-Asian and Dutch-European type 2 diabetic patients to compare differences in the incidence of microalbuminuria and progression of renal failure between both ethnic groups.

We used the registry of the outpatient diabetic clinic of the Haga Teaching Hospital during the period of 1994–1996. Ethnicity was by self-report. Migrants who originally descend from the Indian subcontinent were reported as South-Asian. Patients who were of Dutch descent were reported as European. We selected a cohort of 149 South Asian type 2 diabetic patients and matched them for sex and level of urinary albumin excretion …
Excretion of Lipoteichoic Acid by Group A Streptococci
Authors: Michael L. Alkan, Edwin H. Beachey
Journal: Journal of Clinical Investigation (1978)

Group A streptococci were grown in the presence of [2-3H]glycerol. Concentrated suspensions of the labeled organisms were incubated with and without penicillin. [3H]Glycerol-labeled material accumulated in the supernates in increasing amounts with increasing concentrations of penicillin, ranging from 0 to 50 U/ml. The excretion of labeled material occurred in the absence of nucleic acid synthesis or bacteriolysis indicating that the phenomenon is independent of cell multiplication or decay. The accumulation of label was paralleled by an accumulation of erythrocyte-sensitizing material measured by passive hemagglutination tests for lipoteichoic acid antigen, indicating that a portion of the labeled material possessed the properties of lipoteichoic acid. Culture supernates were fractionated by column chromatography, and the materials obtained were analyzed by electrophoresis on sodium dodecyl sulfate polyacrylamide, thin-layer chromatography, and paper chromatography. The ability of the same materials to bind to human erythrocytes and epithelial cells was tested. The culture supernate contained lipoteichoic acid, deacylated lipoteichoic acid, glycerol phosphate, and free glycerol. Penicillin caused an increase in the amounts of each of the excreted materials. Streptococci that were stimulated with penicillin to lose their lipoteichoic acid (previously shown to mediate adherence of group A streptococci) lost their ability to adhere to buccal mucosal cells, suggesting that penicillin may influence bacterial ecology by mechanisms other than killing sensitive organisms.
<i>Recherches Cliniques et Therapeutiques sur l'Epilepsie, l'Hysterie et l'Idiotie.</i>Compte-Rendu du Service des Enfants Idiots, Epileptiques et Arrieres de Bicetre Pendant l'Annee, 1898, par Bourneville, Avec la Collaboration de MM. Cestan, Chapotin, Katz, Noir (J.), Philippe, Sebilleau et Boyer (J.). Vol. XIX. F. Alcan, Paris, 1899
Authors: W. P. Spratling
Journal: American Journal of Psychiatry (1899)
Isopotential Body Surface Maps and Their Relationship to Atrial Potentials in the Dog
Authors: TERRY D. KING, ROGER C. BARR, G. SCOTT Herman-Giddens, DAVID E. BOAZ, MADISON S. SPACH
Journal: Circulation Research (1972)

The origin of body surface P waves was evaluated in the intact dog by recording body surface isopotential maps and atrial epicardial potential maps. P waves were recorded from 150 points on the body surface, and 80 atrial unipolar electrograms were recorded by means of permanently implanted atrial electrodes during normal sinus rhythm and during atrial pacing. When the atrial pacing sites were changed, the associated shape changes in body surface P waves were highly dependent on the position of the recording sites. Throughout most of the P wave, multiple maxima were present on the body surface, and these were caused by widely separated right and left atrial excitation waves; however, the presence of several simultaneous atrial excitation waves could not be appreciated from the body surface maps when the atrial excitation waves were close to one another. In the last third of atrial excitation there were two maxima on the body surface, one due to atrial excitation waves and the other due to early atrial repolarization. In contrast to the more complicated patterns during excitation, during the P-R segment a single maximum and a single minimum were present on the body surface. The sequence of potential changes on both body surface and atrial epicardium during repolarization was similar to the sequence of excitation except that there was reversed polarity.
Cisplatin, 5-fluorouracil, and cetuximab (PFE) with or without cilengitide in recurrent/metastatic squamous cell carcinoma of the head and neck: results of the randomized phase I/II ADVANTAGE trial (phase II part)
Authors: J.B. Vermorken, F. Peyrade, J. Krauss, R. Mesía, E. Remenar, T.C. Gauler, U. Keilholz, J.P. Delord, P. Schafhausen, J. Erfán, T.H. Brümmendorf, L. Iglesias, U. Bethe, C. Hicking, P.M. Clement
Journal: Annals of Oncology (2014)

Recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) overexpresses αvβ5 integrin. Cilengitide selectively inhibits αvβ3 and αvβ5 integrins and is investigated as a treatment strategy.
Cardiovascular toxicity following sunitinib therapy in metastatic renal cell carcinoma: a multicenter analysis
Authors: G. Di Lorenzo, R. Autorino, G. Bruni, G. Cartenì, E. Ricevuto, M. Tudini, C. Ficorella, C. Romano, M. Aieta, A. Giordano, M. Giuliano, A. Gonnella, C. De Nunzio, M. Rizzo, V. Montesarchio, M. Ewer, S. De Placido
Journal: Annals of Oncology (2009)

Recent data have shown that cardiotoxicity represents a potentially important side-effect in patients treated with sunitinib. We reviewed cardiac adverse events in patients with metastatic renal cell carcinoma (RCC) who underwent treatment with this agent.The medical records of 175 patients with metastatic RCC treated with sunitinib at eight Italian institutions were retrospectively reviewed. Alterations in left ventricular ejection fraction (LVEF) and blood pressure were evaluated. Patients with preexisting cardiac risk factors were specifically scrutinized for increased expression of cardiac changes.Grade 3 hypertension was seen in 17 patients (9.7%); in 12 of these 17, hypertension developed after receiving the third sunitinib cycle. Among these 17 patients, 12 (70.6%) also experienced left ventricular systolic (LVEF) dysfunction; in all, 33 of the 175 patients (18.9%) developed some degree of cardiac abnormality, of which 12 were classified as grade 3 LVEF dysfunction and/or congestive heart failure (CHF) (6.9%). Significant univariate associations for predictors of CHF were history of hypertension (P = 0.008), history of coronary heart disease (P = 0.0005) and prior treatment with an angiotensin-converting enzyme inhibitor (P = 0.04). Multivariate analysis suggested that a history of coronary artery disease [odds ratio (OR) 18, 95% confidence interval (CI) 4-160, P = 0.005] and hypertension (OR 3, 95% CI 1.5-80, P = 0.04) was the only significant independent predictors of CHF.Patients undergoing sunitinib, especially those with a previous history of hypertension and coronary heart disease, are at increased risk for cardiovascular events and should be monitored for exacerbations of their hypertension and for evidence of LVEF dysfunction during treatment.
Effect of β<sub>2</sub>-agonists on Histamine-induced Airway Microvascular Leakage in Ozone-exposed Guinea Pigs
Authors: HIROMASA INOUE, HISAMICHI AIZAWA, KOICHIRO MATSUMOTO, MUTSUMI SHIGYO, SHOHEI TAKATA, MASATO HARA, NOBUYUKI HARA
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

beta 2-adrenergic agonists exhibit antipermeability effects in the airways. However, it is not known whether beta 2-agonists have this beneficial effect in airway mucosa that is already inflamed. We evaluated the effects of two inhaled beta 2-agonists, salbutamol and formoterol, on the histamine-induced bronchoconstriction and plasma extravasation in the airways of guinea pigs with or without ozone exposure. Total pulmonary resistance (RL) was measured before and after histamine inhalation in anesthetized animals that were pretreated with inhaled salbutamol, formoterol, or saline. Plasma extravasation in the airways was measured using Evans blue dye. In the control animals not exposed to ozone, salbutamol and formoterol each significantly reduced both the histamine-induced bronchoconstriction and the plasma extravasation in the trachea and main bronchi. In the ozone-exposed animals, the increase in RL after histamine was greater than that in control animals. Salbutamol and formoterol each significantly reduced histamine-induced bronchoconstriction, even in the ozone-exposed animals. Salbutamol did not affect the histamine-induced plasma extravasation, whereas formoterol reduced the plasma extravasation in the main bronchi, but not in the trachea, of the animals exposed to ozone. These results suggest that the anti-inflammatory properties of formoterol in inflamed airways may contribute to the beneficial effects in the treatment of airway inflammation.
Selective Alteration of Personality and Social Behavior by Serotonergic Intervention
Authors: B Knutson, O M Wolkowitz, S W Cole, T Chan, E A Moore, R C Johnson, J Terpstra, R A Turner, V I Reus
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The authors sought to test the causal hypothesis that serotonergic function modulates aspects of the normal spectrum of individual differences in affective experience and social behavior in humans. METHOD: A selective serotonin reuptake inhibitor (SSRI), paroxetine, 20 mg/day (N=26), or placebo (N=25) was administered to normal volunteers in a double-blind manner for 4 weeks, and personality variables and social behavior were assessed at baseline and at weeks 1 and 4 of treatment. RESULTS: Relative to placebo, SSRI administration reduced focal indices of hostility through a more general decrease in negative affect, yet did not alter indices of positive affect. In addition, SSRI administration increased a behavioral index of social affiliation. Changes in both negative affect and affiliative behavior were significantly related to volunteers' plasma SSRI levels at the end of the experiment. CONCLUSIONS: Central serotonergic function may modulate a dimension of normal personality characterized by reduced negative affective experience and increased affiliative behavior. SSRI administration has significant and detectable effects on these measures even in the absence of baseline clinical depression or other psychopathology.
Oxaliplatin, Fluorouracil, and Leucovorin for Patients With Unresectable Liver-Only Metastases From Colorectal Cancer: A North Central Cancer Treatment Group Phase II Study
Authors: Steven R. Alberts, William L. Horvath, William C. Sternfeld, Richard M. Goldberg, Michelle R. Mahoney, Shaker R. Dakhil, Ralph Levitt, Kendrith Rowland, Suresh Nair, Daniel J. Sargent, John H. Donohue
Journal: Journal of Clinical Oncology (2005)

Surgical resection of liver-only metastases from colorectal cancer has undergone extensive evaluation and review. The use of neoadjuvant chemotherapy to improve the likelihood of resection in disease that is not optimally resectable has not been as well studied.Patients with liver-only metastases from colorectal cancer deemed not optimally resectable by a surgeon with expertise in liver surgery received fluorouracil, leucovorin, and oxaliplatin (FOLFOX4). Patients were periodically reassessed for resectability. Surgical response was classified as completely resectable (S-CR), partially resectable (S-PR), or unresectable (S-UR). Study design specified the accrual of 39 patients, with two or more S-CRs considered evidence of promising activity with respect to increasing the S-CR rate.Forty-two of 44 patients were assessable for this analysis. Twenty-five patients (60%) had tumor reduction by serial imaging. Seventeen patients (40%) underwent surgery (S-CR, n = 14; S-PR, n = 1; and S-UR, n = 2) after a median of 6 months of chemotherapy. With a median postsurgical follow-up of 22 months (range, 13 to 32 months), 11 recurrences have occurred in the 15 S-CR and S-PR patients. Median survival time was 26 months.Our data suggest that FOLFOX4 has a high response rate (complete response, partial response, or reduction) in patients with liver-only metastases from colorectal cancer, allowing for successful resection of disease in a portion of patients initially not judged to be optimally resectable. However, a high recurrence rate after surgery was observed, which, in 73% of patients, involved the liver. Further trials are indicated based on the promising results observed in this trial.
Kidney-Targeted Birt-Hogg-Dube Gene Inactivation in a Mouse Model: Erk1/2 and Akt-mTOR Activation, Cell Hyperproliferation, and Polycystic Kidneys
Authors: M. Baba, M. Furihata, S.-B. Hong, L. Tessarollo, D. C. Haines, E. Southon, V. Patel, P. Igarashi, W. G. Alvord, R. Leighty, M. Yao, M. Bernardo, L. Ileva, P. Choyke, M. B. Warren, B. Zbar, W. M. Linehan, L. S. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2008)

BackgroundPatients with Birt-Hogg-Dubé (BHD) syndrome harbor germline mutations in the BHD tumor suppressor gene that are associated with an increased risk for kidney cancer. BHD encodes folliculin, a protein that may interact with the energy- and nutrient-sensing 5′-AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling pathways.