tbuckley/cabot-search huggingface dataset:
Diallyl trisulfide induced apoptosis in human prostate cancer cells is mediated by inactivation of Akt
Authors: Dong Xiao, Shivendra V. Singh
Journal: Cancer Research (2005)

2459   Epidemiological studies have concluded that dietary intake of allium vegetables, especially garlic, may lower the risk of different types of malignancies including cancer of the prostate, which is the second leading cause of cancer related deaths among men in the United States. Cancer protective effect of allium vegetables is attributed to organosulfur compounds (OSCs), such as diallyl trisulfide (DATS; CH 2 =CH-CH 2 -(S) 3 -CH 2 -CH=CH 2 ), which are generated upon processing (e.g., cutting or chewing) of these vegetables. Recent studies have indicated that in addition to inhibition of chemically induced cancers in animal models, garlic-derived OSCs including DATS can suppress proliferation of cancer cells in culture by causing apoptosis. However, the sequence of events leading to OSC-induced cell death is poorly defined. In our previous study, we found that DATS-induced cell death in human prostate cancer cells was associated with c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)-mediated phosphorylation of Bcl-2, which reduced heterodimer complex formation between Bcl-2 and Bax leading to activation of caspase-9 and caspase-3. However, pharmacological inhibition of JNK or ERK activation offered only partial protection against cell death caused by DATS. These results suggested involvement of additional mechanisms in DATS-induced apoptosis. The present study demonstrates that inactivation of Akt, a kinase implicated in cell survival, is a key event in DATS-induced apoptosis in PC-3 and DU145 human prostate cancer cells. Treatment of PC-3 and DU145 cells resulted in dephosphorylation of Akt (Ser473) and inhibition of its kinase activity. The phosphorylation of Bad, a downstream target of Akt, was also reduced upon treatment with DATS. Inactivation of Akt in both cell lines was due to down-regulation of IGF-IR and dephosphorylation of phosphatidylinositol-3’-kinase (an upstream effector of Akt). Ectopic expression of constitutively active Akt in DU145 cells offered significant protection against DATS-induced cell death. In conclusion, the results of the present study indicate that DATS-induced apoptosis in human prostate cancer cells is, at least in part, caused by inhibition of Akt (supported by NIH grants CA101753 and CA076348).
Comparison of female to male and male to female transmission of HIV in 563 stable couples. European Study Group on Heterosexual Transmission of HIV.
Authors: Johnson
Journal: BMJ (1992)

OBJECTIVE--To identify risk factors for heterosexual transmission of HIV and to compare the efficiency of male to female and female to male transmission. DESIGN--Cohort study of heterosexual couples. Regular partners of HIV infected subjects were tested and both members of the couples interviewed every six months. HIV prevalence in partners was analysed according to the characteristics of the couples. SETTING--Nine European countries. SUBJECTS--563 couples comprising 156 female index patients with their 159 male partners and 400 male index patients with their 404 female partners. Partners reporting risk factors other than sexual contacts with the index patient were excluded. MAIN OUTCOME MEASURES--HIV infection in partners and high risk sexual behaviour. RESULTS--Overall, 19 (12%) male partners and 82 (20%) female partners were infected with HIV, suggesting that male to female transmission is 1.9 (95% confidence interval 1.1 to 3.3) times more effective than female to male transmission. An advanced stage of HIV infection in the index patient (odds ratio 17.6; 4.9 to 62.7) and sexual contacts during menses (3.4; 1.0 to 11.1) increased the risk of female to male transmission and stage of infection (2.7; 1.5 to 4.9), anal sex (5.1; 2.9 to 8.9), and age of the female partner (3.9; 1.2 to 13.0 for age > 45 years) increased the risk of male to female transmission. None of the 24 partners who had used condoms systematically since the first sexual contact was infected. CONCLUSIONS--Several factors which potentiate the risk of transmission through unprotected vaginal intercourse have been identified. Knowledge of these factors could be helpful for counselling patients infected with HIV and their sexual partners.
Human Immunodeficiency Virus Type 1 Protease Inhibitor Modulates Activation of Peripheral Blood CD4+ T Cells and Decreases Their Susceptibility to Apoptosis In Vitro and In Vivo
Authors: Elaine M. Sloand, Princy N. Kumar, Sonnie Kim, Aniruddho Chaudhuri, Frank F. Weichold, Neal S. Young
Journal: Blood (1999)
Anticancer Effects of Melatonin and Omega-3 Fatty Acids on Inhibition of Fatty Acid Transport in Human Cancer Xenograft-Bearing Nude Rats Occur via Receptor-Mediated Signal Transduction.
Authors: Erin Dauchy, Robert Dauchy, Robert Tirrell, Leslie Davidson, Jean Krause, Paul Tirrell, Leonard Sauer, David Blask
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4478 

Melatonin (MLT), the pineal neurohormone secreted primarily at night in mammals, and omega-3 fatty acids (FAs) regulate linoleic acid (LA)-dependent growth in several rodent and human tumors in vivo . In tissue-isolated hepatoma 7288CTC and human MCF-7 steroid responsive and non-responsive tumors perfused in situ with arterial blood, MLT and eicosapentaenoic acid (EPA, omega-3 FA) inhibit LA-uptake and conversion to 13-hydroxyoctadecadienoic acid (13-HODE), a lipoxygenase product that stimulates EGF mitogenesis. The present study explores the effects of dietary intake of MLT (50 μg/day)/fish oil (5% FO) diet have on the growth and metabolism of tissue-isolated human PC3 prostate and FaDu hypopharyngeal squamous cell xenografts in nude rats. Control PC3 and FaDu tumor-bearing rats, raised on 5 % corn oil (CO) diet revealed tumor latency-to-onset and growth rates, respectively, of 18 and 26 days and 0.61 ± 0.08 and 0.46 ± 0.46 ± 0.06 g/day; final mean tumor weights were 6.2 ± 0.7 (PC3) and 6.0 ± 0.6 g (FaDu), respectively. LA uptake and 13-HODE release by PC3 and FaDu tumors were 7.9 ± 3.2 and 8.1 ± 2.4 μg/min/g, and 20.4 ± 3.8 and 18.5 ± 0.9 nmol/min/g, respectively. Incorporation of 3H-thymidine and DNA content for the PC3 and FaDu xenografts were 51.0 ± 4.9 and 61.6 ± 5.5 dpms/μg DNA, respectively, and 2.6 ± 0.2 and 4.0 ± 0.07 μg/g tumor. No tumors grew in animals raised on 5% FO/MLT diet. PC3 and FaDu tumors perfused in situ with donor animal blood augmented with either 1nM MLT or 0.4 mM EPA (plasma concentration) showed a complete inhibition of LA uptake, 13-HODE release, Erk 1/2 and MEK activities, and over a 50% reduction in tumor cAMP levels and [3H]thymidine incorporation into tumor DNA. The mean values for pH, PO2, and PCO2, between control and treatment regimens in arterial blood were 7.44 ± 0.02, 155 ± 18, and 32 ± 3, and 7.31 ± 0.03, 33 ± 4, and 57 ± 4 in the tumor venous blood, respectively. The inhibitions occurred via a Gi protein-coupled, cAMP-dependent signal trandsuction pathway and were reversed by forskolin, 8-Br-cAMP, and pertussis toxin.Furthermore, addition of 13-HODE reversed the inhibition of [3H]thymidine incorporation but had no effect on FA uptake. The Western diet contains an overabundance of LA and low amounts of both omega-3 FAs and MLT. Thus, understanding the underlying mechanism of action of these tumor growth-inhibitory agents will strengthen efforts to reduce LA and increase omega-3 and MLT consumption as a new cancer prevention strategy in humans.
Plasma Brain Natriuretic Peptide-Guided Therapy to Improve Outcome in Heart Failure
Authors: Patrick Jourdain, Guillaume Jondeau, François Funck, Pascal Gueffet, Alain Le Helloco, Erwan Donal, Jean F. Aupetit, Marie C. Aumont, Michel Galinier, Jean C. Eicher, Alain Cohen-Solal, Yves Juillière
Journal: Journal of the American College of Cardiology (2007)
Abstract 1913: Distinct eNOS Regulation by Protease-Activated Receptor 1 and 2 Involving Gq, G12/13 and Y27632-Sensitive Non-Rho Kinase
Authors: Akinari Hinoki, Hiroyuki Suzuki, Kunie Eguchi, Sadaharu Higuchi, Keita Kimura, Evangeline D Motley, Vabren Watts, Satoru Eguchi
Journal: Circulation (2008)

Protease-activated receptors (PARs), such as PAR1 and PAR2 have been implicated in the regulation of endothelial nitric oxide (NO) production. We hypothesized that PAR1 and PAR2 distinctly regulate the activity of endothelial NO synthase (eNOS) through the selective phosphorylation of a positive regulatory site, Ser 1179 and a negative regulatory site, Thr 497 . In bovine aortic endothelial cells (BAECs), a PAR1 ligand, TFLLR, phosphorylated eNOS at Thr 497 . It had no effect on Ser 1179 phosphorylation or cyclic GMP (cGMP) production. In contrast, a PAR2 ligand, SLIGRL, phosphorylated Ser 1179 with no noticeable effect on Thr 497 . SLIGRL stimulated cGMP production that was blocked by L-NAME. Neither eNOS phosphorylation nor cGMP production was observed by a PAR4 agonist, AY-NH2. Thrombin has been shown to transactivates PAR2 through PAR1. Thus, thrombin stimulates eNOS phosphorylation at both sites as well as cGMP production in BAECs. Importantly, SLIGRL-induced Ser 1179 phosphory-lation and cGMP production were inhibited by a G q inhibitor, YM-254890. In addition, eNOS phosphorylation was not affected by over-expression of GRK2 C-tail or pertusis toxin pretreatment. By contrast, TFLLR-induced Thr 497 phosphorylation was selectively inhibited by a Rho-kinase inhibitor, Y27632, and over-expression of p115RhoGEF RGS domain, a selective G 12/13 inhibitor. However, other inhibitors (H-1152 and dnRho) that target Rho-kinase or a PKC inhibitor, GF109203X, failed to block TFLLR-induced Thr 497 phosphorylation. Taken together, these data suggest that PAR1-induced phosphorylation of eNOS at Thr 497 requires G 12/13 and subsequent activation of a Y27632-sensitive eNOS Thr 497 kinase that is distinct from Rho-kinase or PKC. We conclude that PAR1 and PAR2 distinctly regulate eNOS activity through G q and G 12/13 , respectively, delineating the novel signaling pathways by which proteases regulate eNOS activity. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 24: The phosphorylation of p53 at serine 46 is essential to induce cell death through palmdelphin in response to DNA damage
Authors: Nurmaa Khund Dashzeveg, Kiyotsugu Yoshida
Journal: Cancer Research (2015)

Abstract Tumor suppressor p53 plays a pivotal role in cell cycle arrest, DNA repair, and apoptosis in response to DNA damage. Promoter selectivity of p53 depends mainly on post-translational modification. Notably, the apoptotic function of p53 is related to its phosphorylation at serine-46 (ser46) to promote pro-apoptotic genes. However, little is known about the pro-apoptotic genes induced by Ser46 phosphorylation. Our research achieved to investigate the pro-apoptotic genes induced by p53 in a phospho-ser46-specific manner using microarray and ChIP sequencing in human cancer cell lines. As a result, palmdelphin (PALMD), an isoform of paralemmin protein, was strongly elicited from the phosphorylation of ser46. The mRNA and protein expression of PALMD increased only in wild type p53 transfected cells, but not in ser46-mutated cells. Importantly, PALMD moved to the nucleus in response to DNA damage and the apoptotic function of PALMD was tightly exerted with localization into nucleus. Interestingly, down-regulation of PALMD by siRNA resulted in necroptosis-like cell death through ATP depletion. Moreover, we found vimentin as a PALMD interacting protein and the depletion of vimentin increased PALMD level to accelerate apoptosis. These results demonstrate that p53 regulates cell death fate (apoptosis or necroptosis-like cell death) through promoting PALMD expression in a phospho-ser46-specific manner in response to DNA damage. Citation Format: Nurmaa Khund Dashzeveg, Kiyotsugu Yoshida. The phosphorylation of p53 at serine 46 is essential to induce cell death through palmdelphin in response to DNA damage. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 24. doi:10.1158/1538-7445.AM2015-24
Abstract 10118: Trends in Renal Complication Rates Among Medicare Beneficiaries Undergoing Percutaneous Coronary Interventions: Fiscal Years 2006 through 2009
Authors: Aaron Kugelmass, David J Cohen, Matthew Reynolds, Phillip Brown, Steven Culler, April W Simon
Journal: Circulation (2011)

Objective: Enhanced attention has focused on contrast induced nephropathy among patients undergoing PCI. This study reports four year trends in the rate of renal complications among Medicare Benefi...
Fluoxetine augmentation of clozapine treatment in patients with schizophrenia
Authors: R W Buchanan, B Kirkpatrick, N Bryant, P Ball, A Breier
Journal: American Journal of Psychiatry (1996)

The authors examined the efficacy of fluoxetine augmentation of clozapine treatment response in schizophrenic outpatients who, despite adequate treatment with clozapine, continued to exhibit persistent positive or negative symptoms.Thirty-three patients completed on 8-week, double-blind, parallel-groups comparison of adjunctive fluoxetine and placebo.There were no significant differences in positive, negative, depressive, or obsessive-compulsive symptoms between patients given adjunctive fluoxetine or placebo.These results suggest that fluoxetine is not effective in augmenting clozapine treatment response.
Several reasons exist for failure of health education message
Authors: S. Thornton, D. Shah, J. Catalan, E. Carlin, F. Boag
Journal: BMJ (1996)

abstained from sex immediately after their diagnosis, for periods ranging from a few months to two years, with a return to sex coinciding with a return of confidence and self esteem and a greater knowledge of the risks involved.Almost all participants observed that the frequency with which they had sex had declined since their diagnosis.Indeed, five men reported that they had not had a sexual relationship since their diagnosis.We are aware that the self selected nature of our sample may have biased the results obtained.Our study strongly suggests, however, that the sexual practices of many HIV positive homo- sexual and bisexual men may not correspond to those described by Catchpole and colleagues.Nevertheless, we agree with the authors' conten- tion that their data highlight the need for more effective health education messages, and we have found that this need was also expressed by the patients we surveyed.
Effect of bromocriptine on affect and libido in hyperprolactinemia
Authors: M. C. S. Koppelman, B. L. Parry, J. A. Hamilton, S. W. Alagna, D. L. Loriaux
Journal: American Journal of Psychiatry (1987)

Six women with primary hyperprolactinemia (mean prolactin level, 50 ng/ml) were matched with six normal women on eight factors influencing life style. Observers blind to endocrine status followed the subjects weekly for 10 weeks. Patients took bromocriptine, 2.5 mg twice daily, or placebo in a randomized double-blind sequence with crossover at 5 weeks. The mean Hamilton score for the patients was compatible with mild depression and higher than that for normal subjects during placebo but not during bromocriptine treatment. Libido was similar in both groups during placebo and bromocriptine. The mean number of orgasms reported per day was lower in patients than in normal subjects during both treatment conditions, although one patient reported orgasms during drug treatment only. Hyperprolactinemia in women may be associated with mild depression and a decrease in orgasmic frequency.
Abstract 93: Universal homogenous bioluminescent assay that monitor the activity various classes of methyltransferases in vitro
Authors: Kevin Hsiao, Said Goueli
Journal: Cancer Research (2015)

Abstract Post transcriptional modifications of proteins and nucleic acids are well-recognized to play major role in influencing cell fate towards cellular proliferation, differentiation, and cell death. Such modifications that include phosphorylation, acetylation, methylation, etc. have been validated as drug targets resulting in the development of several drugs. Recent biochemical and biological data suggest that the enzymatic activities of several of these enzymes have pathogenic roles in cancer, inflammation, and neurodegenerative diseases. Thus, pharmacological modulation of these enzymes by small molecules will be beneficial in developing novel therapeutics for multiple unmet medical needs. Of these, methyltransferases are known to alter the epigenome by altering the methylation status of nucleic acids or proteins resulting in changes in cellular functions. Towards this goal of searching for activators/inhibitors of these enzymes for the development of next generation of drugs, screening assays for these modulators are urgently needed. To address these unmet needs, we have developed a novel assay that monitors the activities of these enzymes and their modulation by small molecules. The assay is bioluminescent based, HTS formatted and highly sensitive. The assay is universal since it is based on monitoring the formation of the universal product S-adenosylhomocysteine (SAH), i.e., capable of detecting changes in activity of a broad range of methyltransferases such as DNA, protein, RNA, and small molecules methyltransferases. In addition, the assay has been validated for all classes of protein methyltransferases (Lysine and Arginine), and with different types of substrates (small peptides, large proteins, or even nucleosomes). This enables determining the specificity of these enzymes and their substrate requirements. The assay has high signal to background and low C.V. The assay is robust (Z’ value &amp;gt; 0.7) and has been validated using various plate densities such as 96-, 384, and 1536-well plates. A strong feature of this assay is its utility with broad range of substrates with no limitations on the use of high concentrations of substrates or the composition of the substrates (short vs. long peptides), thus enabling the generation of kinetic data and determining the mechanism of action of various modulators of methyltransferases of interest. Citation Format: Kevin Hsiao, Said Goueli. Universal homogenous bioluminescent assay that monitor the activity various classes of methyltransferases in vitro. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 93. doi:10.1158/1538-7445.AM2015-93
Impact of urinary tract infections on short-term kidney graft outcome
Authors: M. Bodro, G. Sanclemente, I. Lipperheide, M. Allali, F. Marco, J. Bosch, F. Cofan, M.J. Ricart, N. Esforzado, F. Oppenheimer, A. Moreno, C. Cervera
Journal: Clinical Microbiology and Infection (2015)
P0191 : IFN-free regimens overcome the negative effect of portal hypertension on virologic response and viral kinetics in patients with cirrhosis
Authors: M. Mandorfer, K. Kozbial, C. Freissmuth, P. Schwabl, A.F. Stättermayer, T. Reiberger, S. Beinhardt, R. Schwarzer, M. Trauner, A. Ferlitsch, H. Hofer, M. Peck-Radosavljevic, P. Ferenci
Journal: Journal of Hepatology (2015)
Abstract 15821: Mitogenic and Proinflammatory Actions of Thrombin-regulated P2Y12 ADP Receptor in Human Vascular Smooth Muscle Cells
Authors: Bernhard H Rauch, Swen Ermler, Andreas Bohm, Anke C Rosenkranz, Julia Driessen, Jens W Fischer, Atsuhiro Sugidachi, Joseph A Jakubowski, Karsten Schror
Journal: Circulation (2010)

The platelet ADP receptor P2Y12 contributes to activation of platelets upon vascular injury and is the molecular target of the thienopyridine anti-platelet drugs. Here, we describe for the first ti...
Clozapine for treatment-refractory mania
Authors: J R Calabrese, S E Kimmel, M J Woyshville, D J Rapport, C J Faust, P A Thompson, H Y Meltzer
Journal: American Journal of Psychiatry (1996)

The efficacy of clozapine for treatment-resistant mania was examined in a prospective trial for patients with bipolar or schizoaffective disorder.The subjects were 25 acutely manic patients with either bipolar disorder (N = 10) or schizoaffective disorder-bipolar subtype (N = 15) for whom lithium, anticonvulsants, and neuroleptics had been ineffective, had produced intolerable side effects, or both. After a 7-day washout, the patients were treated with clozapine monotherapy. They were evaluated over 13 weeks with the Young Mania Rating Scale and the Brief Psychiatric Rating Scale (BPRS).Of the 25 patients, 18 (72%) exhibited marked improvement on the Young Mania Rating Scale, and eight (32%) exhibited marked improvement on the BPRS. The bipolar patients as compared to schizo-affective patients, and the nonrapid as compared to rapid cyclers, had significantly greater improvement in total BPRS score.These results suggest that clozapine is an effective therapy for treatment-resistant bipolar and schizoaffective mania.
Risk of intraocular haemorrhage remains unknown
Authors: S. Fava, J. Azzopardi, H. A. Muscat, F. F Fenech
Journal: BMJ (1995)

EDITOR,—Helen Ward and John S Yudkin conclude that thrombolysis should not be withheld in diabetic patients with retinopathy.1 We have shown that diabetic subjects are less likely to receive this treatment than non-diabetic controls.2

The authors note that there has been only …
Cerebral oedema after MDMA ("ecstasy") and unrestricted water intake
Authors: T M Cook
Journal: BMJ (1996)

ent from the international non-proprietary name.On the other hand, the World Health Organisation cannot impose on these countries a name that they consider to be unacceptable.The most logical solution would be to set up bilateral discussions between the organisation's experts and the national nomenclature committees with a view to the adoption of a single non- proprietary name for those drugs for which discrepancies exist.
Single Sample Application of the EMC92/SKY92 Signature Using the Mmprofiler
Authors: Martin H. Van Vliet, Rowan Kuiper, Belinda Dumee, Leonie de Best, Peter J. van der Spek, Emmanuel M.E.H. Lesaffre, Mark van Duin, Anders Waage, Sonja Zweegman, Pieter Sonneveld, Erik H. van Beers
Journal: Blood (2014)
Abstract 10978: MDCO-216 (Apo A-I Milano/POPC Complex) Administered to Cynomolgus Monkeys Induces Pronounced Changes in Plasma Lipids and Apolipoproteins
Authors: Herman J Kempen, S. E Bellibas, Brad Zerler, Stephanie Plassmann, Dimitrios Goundis, Peter Wijngaard
Journal: Circulation (2011)
Meat and Livestock Commission's advertising campaign
Authors: C. Lamb
Journal: BMJ (1996)

these animals had died of bovine spongiform encephalopathy,7 although the details of the experiment have not been published.Furthermore, since the ban on cannibalistic feeding was imposed in 1988 over 22000 animals have been bom that have subsequently developed bovine spongiform encephalopathy; one was born as recently as June 1993.Interestingly, the range of ages at which the disease was diagnosed in these animals is virtually the same as that in animals born before the ban (table).Distribution of ages of animals with confirmed bovine spongiform encephalopathy bom before and after feed containing recycled animal remains was banned in July 1988.Figures are numbers (percentages) Born before ban, Born after ban, Age disease diagnosed disease diagnosed (years) 19893