tbuckley/cabot-search huggingface dataset:
Polyunsaturated Fatty Acids Are Cerebral Vasodilators via the TREK-1 Potassium Channel
Authors: Nicolas Blondeau, Olivier Pétrault, Stella Manta, Valérie Giordanengo, Pierre Gounon, Régis Bordet, Michel Lazdunski, Catherine Heurteaux
Journal: Circulation Research (2007)

Vessel occlusion is the most frequent cause for impairment of local blood flow within the brain resulting in neuronal damage and is a leading cause of disability and death worldwide. Polyunsaturated fatty acids and especially alpha-linolenic acid improve brain resistance against cerebral ischemia. The purpose of the present study was to evaluate the effects of polyunsaturated fatty acids and particularly alpha-linolenic acid on the cerebral blood flow and on the tone of vessels that regulate brain perfusion. alpha-Linolenic acid injections increased cerebral blood flow and induced vasodilation of the basilar artery but not of the carotid artery. The saturated fatty acid palmitic acid did not produce vasodilation. This suggested that the target of the polyunsaturated fatty acids effect was the TREK-1 potassium channel. We demonstrate the presence of this channel in basilar but not in carotid arteries. We show that vasodilations induced by the polyunsaturated fatty acid in the basilar artery as well as the laser-Doppler flow increase are abolished in TREK-1(-/-) mice. Altogether these data indicate that TREK-1 activation elicits a robust dilation that probably accounts for the increase of cerebral blood flow induced by polyunsaturated fatty acids such as alpha-linolenic acid or docosahexanoic acid. They suggest that the selective expression and activation of TREK-1 in brain collaterals could play a significant role in the protective mechanisms of polyunsaturated fatty acids against stroke by providing residual circulation during ischemia.
Cryopreservation of oocytes from pre-antral follicles
Authors: C. A. Amorim
Journal: Human Reproduction Update (2003)

Cryobiology is a very important tool in reproductive biology. Research in this area focuses on the possibility of restoring fertility in women with reproductive problems or after cancer treatments. Another goal is to establish a genetic resource bank for endangered or commercially important animal species. Cryopreservation of oocytes from pre-antral follicles has been studied during the past decade. Procedures can be divided between the cryopreservation of either ovarian tissue or isolated follicles. Most studies describe a slow freezing/rapid thawing protocol to cryopreserve ovarian fragments. Histology shows that the follicles maintain their morphological integrity, and transplantation of ovarian tissue demonstrates that the follicles can restart their growth and eventually ovulate. Some research groups have obtained offspring using this procedure in mice and sheep. With regard to the cryopreservation of isolated follicles, the few studies reported in this area used the same freezing protocol, and some of them described follicular growth using in-vitro culture. The best result was obtained in mice, with animal birth after follicular cryopreservation and culture. However, additional studies are necessary for a better understanding of the events during follicular cryopreservation and to establish a standard protocol for ovarian transplantation or follicle culture.
Frontal White Matter Microstructure and Treatment Response of Late-Life Depression: A Preliminary Study
Authors: George S Alexopoulos, Dimitris N Kiosses, Steven J Choi, Christopher F Murphy, Kelvin O Lim
Journal: American Journal of Psychiatry (2002)

This study tested the hypothesis that microstructural abnormalities in white matter areas of the brain containing frontostriatal tracts are associated with a low rate of remission of geriatric depression.Thirteen older patients with major depression received open, but controlled, treatment with citalopram at a target daily dose of 40 mg for 12 weeks. Diffusion tensor imaging was used to determine fractional anisotropy in preselected white matter regions.Survival analysis with Cox's proportional hazards model revealed that lower fractional anisotropy of the right and the left frontal white matter regions 15 mm above the anterior commissure-posterior commissure plane was associated with a low remission rate after age was considered. Remission was not significantly associated with fractional anisotropy of lower frontal regions or a temporal region.Microstructural white matter abnormalities lateral to the anterior cingulate may be associated with a low rate of remission of geriatric depression.
ATDC/TRIM29 Phosphorylation by ATM/MAPKAP Kinase 2 Mediates Radioresistance in Pancreatic Cancer Cells
Authors: Lidong Wang, Huibin Yang, Phillip L. Palmbos, Gina Ney, Taylor Ann Detzler, Dawn Coleman, Jacob Leflein, Mary Davis, Min Zhang, Wenhua Tang, J. Kevin Hicks, Corey M. Helchowski, Jayendra Prasad, Theodore S. Lawrence, Liang Xu, Xiaochun Yu, Christine E. Canman, Mats Ljungman, Diane M. Simeone
Journal: Cancer Research (2014)

Pancreatic ductal adenocarcinoma (PDAC) is characterized by therapeutic resistance for which the basis is poorly understood. Here, we report that the DNA and p53-binding protein ATDC/TRIM29, which is highly expressed in PDAC, plays a critical role in DNA damage signaling and radioresistance in pancreatic cancer cells. Ataxia-telangiectasia group D-associated gene (ATDC) mediated resistance to ionizing radiation in vitro and in vivo in mouse xenograft assays. ATDC was phosphorylated directly by MAPKAP kinase 2 (MK2) at Ser550 in an ATM-dependent manner. Phosphorylation at Ser-550 by MK2 was required for the radioprotective function of ATDC. Our results identify a DNA repair pathway leading from MK2 and ATM to ATDC, suggesting its candidacy as a therapeutic target to radiosensitize PDAC and improve the efficacy of DNA-damaging treatment.
Karyotypic Derivation of H9 Cell Line Expressing Human Immunodeficiency Virus Susceptibility
Authors: T R Chen
Journal: JNCI Journal of the National Cancer Institute (1992)

Background : The T-cell lymphoma HUT78 cell line and the H9 clone of the CD4-positive HT cell line, derived from HUT78, are known to be genetically identical on the basis of allozyme (allelic isozyme) patterns and DNA fingerprinting, but the chromosome compositions of these cell lines have not been determined. The HT cell line and its H9 clone carry susceptibility to the human immunodeficiency virus (HIV). Purpose : The purpose of this study was to examine specific chromosome changes linking the expression of the HIV susceptibility that is unique to H9 cells by characterizing the karyo-types of the HUT78 and the H9 cell lines, by comparing chromosome differences between these lines, and by evaluating the relationships between them. Methods : Air-dried chromosome slides were prepared, and the fast Giemsa-trypsin method was used to delineate G-bands. The numerical distribution of chromosomes from the two cell lines was determined, and complete chromosome analysis in 47 HUT78 metaphases and 21 H9 metaphases with discernible G-banding was used to specify the modal karyotypes of each cell line. Results : Both cell lines had complex karyotypes that contained 47%–65% structurally modified marker chromosomes. The distribution of numbers of chromosomes in HUT78 cultures was broad. There were two distinct modal numbers of chromosomes at 42 and 43 and at 73, resulting from the presence of three actively growing sublines: two hypodiploid (1 s ) sublines (HUT78/1 s A and HUT78/1 s B) and a hypertriploid (2 s ) subline (HUT78/2 s ), respectively. HUT78/1 s A and HUT78/1 s B differed by five reciprocal chromosome replacements, and HUT78/2 s had double copies of most of the chromosomes in 1 s cells. H9 and HUT78/2 s had had 21 matching markers, 10 of which were paired; contained 21 chromosomes with the same number of copies; consistently lacked eight homologous normal chromosomes; and showed close modal numbers of chromosomes at 69 and 73, respectively. Conclusions : Derivation of the 2 s subline from the Is subline by poly-ploidization is apparent. All lines apparently had the same progenitor cell population, and HUT78/2 s represents an intermediate linking HUT78/15 to H9. Implications : These data should be useful for studying specific chromosome changes linking the expression of the HIV susceptibility unique to H9 cells. Karyologic studies such as those presented here can provide data ( a ) to clearly identify the clonal cell population of a subline, ( b ) to examine relationships among sublines of the same progenitor, and ( c ) to provide a clue that may link a subtle chromosome change to a phenotypic expression. [J Natl Cancer Inst 84:1922–1926, 1992]
Clinical Pharmacokinetics of Amifostine and WR1065 in Pediatric Patients with Medulloblastoma
Authors: Trevor McKibbin, John C. Panetta, Maryam Fouladi, Amar Gajjar, Feng Bai, M. Fatih Okcu, Clinton F. Stewart
Journal: Clinical Cancer Research (2010)

We evaluated the pharmacokinetics of amifostine and WR1065 in pediatric patients with newly diagnosed medulloblastoma to assess the influence of patient covariates, including demographics, clinical characteristics, and genetic polymorphisms, on amifostine and WR1065 pharmacokinetic parameters.
Chemical Carcinogenesis in Nude Mice: Comparison Between Nude Mice From Homozygous Matings and Heterozygous Matings and Effect of Age and Carcinogen Dose&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: O Stutman
Journal: JNCI Journal of the National Cancer Institute (1979)

The incidence and latency periods for local tumor development after sc injection of 3-methylcholanthrene (MCA) into 30-day-old nude mice (nu/nu partially inbred on the CBA/H background) derived from homozygous matings (nu/nu times nu/nu) or heterozygous matings (nu/+ times nu/+) were comparable and did not differ with the immunologically normal controls, even when the carcinogen dosages ranged from 0.01 to 0.10 mg. Similarly, no differences in tumor incidence or latency periods between nude mice from homozygous or heterozygous matings as well as their immunologically normal controls were observed when weight-adjusted doses of MCA equivalent to 0.02 to 0.10 mg in the 30-day-old mice were administered at 120, 210, or 360 days of age. Tumor incidence was lower in nude mice and normal mice when MCA was administered at 210 and 360 days of age, especially in mice given the lower dose of MCA. The lower dosages of MCA (0.01-0.05 mg) had no detectable immunodepressive effects in normal mice. Thus the "normal" tumor incidence in nude mice after MCA administration could not be attributed to: 1) the effect of humoral thymus gland function (in the nude mice derived from heterozygous matings), 2) the immunodepressive effects of the carcinogen (the lower MCA dosages are not immunodepressive), or 3) the age of the mice at administration. These results argue against the thymus dependency of immunologic surveillance.
Phosphorylation of HOX11/TLX1 on Threonine-247 during mitosis modulates expression of cyclin B1
Authors: Edwin Chen, Xiaoyong Huang, Yanzhen Zheng, You-Jun Li, Alden Chesney, Yaacov Ben-David, Eric Yang, Margaret R Hough
Journal: Molecular Cancer (2010)

Abstract Background The HOX11/TLX1 (hereafter referred to as HOX11) homeobox gene was originally identified at a t(10;14)(q24;q11) translocation breakpoint, a chromosomal abnormality observed in 5-7% of T cell acute lymphoblastic leukemias (T-ALLs). We previously reported a predisposition to aberrant spindle assembly checkpoint arrest and heightened incidences of chromosome missegregation in HOX11-overexpressing B lymphocytes following exposure to spindle poisons. The purpose of the current study was to evaluate cell cycle specific expression of HOX11. Results Cell cycle specific expression studies revealed a phosphorylated form of HOX11 detectable only in the mitotic fraction of cells after treatment with inhibitors to arrest cells at different stages of the cell cycle. Mutational analyses revealed phosphorylation on threonine-247 (Thr247), a conserved amino acid that defines the HOX11 gene family and is integral for the association with DNA binding elements. The effect of HOX11 phosphorylation on its ability to modulate expression of the downstream target, cyclin B1, was tested. A HOX11 mutant in which Thr247 was substituted with glutamic acid (HOX11 T247E), thereby mimicking a constitutively phosphorylated HOX11 isoform, was unable to bind the cyclin B1 promoter or enhance levels of the cyclin B1 protein. Expression of the wildtype HOX11 was associated with accelerated progression through the G2/M phase of the cell cycle, impaired synchronization in prometaphase and reduced apoptosis whereas expression of the HOX11 T247E mutant restored cell cycle kinetics, the spindle checkpoint and apoptosis. Conclusions Our results demonstrate that the transcriptional activity of HOX11 is regulated by phosphorylation of Thr247 in a cell cycle-specific manner and that this phosphorylation modulates the expression of the target gene, cyclin B1. Since it is likely that Thr247 phosphorylation regulates DNA binding activity to multiple HOX11 target sequences, it is conceivable that phosphorylation functions to regulate the expression of HOX11 target genes involved in the control of the mitotic spindle checkpoint.
Inhibition of Phosphodiesterase Type 5 by the Activator of Nitric Oxide–Sensitive Guanylyl Cyclase BAY 41-2272
Authors: Florian Mullershausen, Michael Russwurm, Andreas Friebe, Doris Koesling
Journal: Circulation (2004)

Background— By the formation of cGMP, nitric oxide (NO)–sensitive guanylyl cyclase (GC) acts as the effector for the signaling molecule NO and mediates the relaxation of vascular smooth muscle and the inhibition of platelet aggregation. The compounds YC-1 and BAY 41-2272 are regarded as NO-independent activators and sensitizers of NO-sensitive GC. In vivo effects, for example, lowering blood pressure and prolonging tail-bleeding times, turn the compounds into promising candidates for the therapy of cardiovascular diseases. However, YC-1 has also been shown to inhibit the major cGMP-degrading enzyme phosphodiesterase type 5 (PDE5). The synergistic properties of YC-1 on cGMP formation and degradation lead to an excessive NO-induced cGMP accumulation in cells, explaining the observed physiological effects. We assessed a potential inhibition of PDE5 by the new GC activator BAY 41-2272. Methods and Results— The effects of BAY 41-2272 on NO-sensitive GC and PDE5 activities were tested in vitro. BAY 41-2272 not only sensitized NO-sensitive GC toward activation by NO but also, with comparable potency, inhibited cGMP degradation by PDE5. In intact platelets, BAY 41-2272 greatly potentiated the NO-induced cGMP response that was caused by a synergistic effect of BAY 41-2272 on cGMP formation and degradation. Conclusions— The physiological effects of BAY 41-2272, which are commonly ascribed to the NO-independent activation of NO-sensitive GC, are rather due to the synergism of sensitization of NO-sensitive GC and inhibition of PDE5.
Comparison between exhaled and sputum oxidative stress biomarkers in chronic airway inflammation
Authors: M. Corradi, P. Pignatti, P. Manini, R. Andreoli, M. Goldoni, M. Poppa, G. Moscato, B. Balbi, A. Mutti
Journal: European Respiratory Journal (2004)

The aim of the present study was to compare aldehyde levels resulting from lipid peroxidation in exhaled breath condensate (EBC) and induced sputum (IS) supernatant of subjects with asthma and chronic obstructive pulmonary disease (COPD). Aldehydes (malondialdehyde (MDA), acrolein, n -hexanal (C6), n -heptanal (C7), n -nonanal (C9), 4-hydroxynonenal (HNE) and 4-hydroxyhexenal (HHE)) in both biological fluids were measured by liquid chromatography-tandem mass spectrometry. MDA concentrations in sputum were 132.5 nM (82.5–268.8) and 23.7 nM (9–53.7) in EBC. Similarly, C6, C7 and C9 concentrations in IS were 1.5–4.7-fold higher than in EBC. Acrolein levels were 131.1 nM (55.6–264.6) in IS and 45.3 nM (14.4–127.1) in EBC. The concentrations of HNE and HHE in IS were not significantly different from the levels in EBC. Aldehyde levels in EBC did not show any correlation with aldehyde levels in IS or with differential sputum cellular count. In COPD, MDA in EBC, but not its IS counterpart, was negatively correlated with the severity of disease. In conclusion, the data presented here show that aldehydes can be detected in both exhaled breath condensate and supernatant of induced sputum, but that their relative concentrations are different and not correlated with each other. Therefore, with regard to lipid peroxidation products, exhaled breath condensate and induced sputum must be considered as independent techniques.
Co-binding by YY1 identifies the transcriptionally active, highly conserved set of CTCF-bound regions in primate genomes
Authors: Petra C Schwalie, Michelle C Ward, Carolyn E Cain, Andre J Faure, Yoav Gilad, Duncan T Odom, Paul Flicek
Journal: Genome biology (2013)

The genomic binding of CTCF is highly conserved across mammals, but the mechanisms that underlie its stability are poorly understood. One transcription factor known to functionally interact with CTCF in the context of X-chromosome inactivation is the ubiquitously expressed YY1. Because combinatorial transcription factor binding can contribute to the evolutionary stabilization of regulatory regions, we tested whether YY1 and CTCF co-binding could in part account for conservation of CTCF binding.Combined analysis of CTCF and YY1 binding in lymphoblastoid cell lines from seven primates, as well as in mouse and human livers, reveals extensive genome-wide co-localization specifically at evolutionarily stable CTCF-bound regions. CTCF-YY1 co-bound regions resemble regions bound by YY1 alone, as they enrich for active histone marks, RNA polymerase II and transcription factor binding. Although these highly conserved, transcriptionally active CTCF-YY1 co-bound regions are often promoter-proximal, gene-distal regions show similar molecular features.Our results reveal that these two ubiquitously expressed, multi-functional zinc-finger proteins collaborate in functionally active regions to stabilize one another's genome-wide binding across primate evolution.
Grand Mal Epileptic Seizures During Ciprofloxacin Therapy
Authors: Ivan L. Slavich
Journal: JAMA (1989)

To the Editor.—  Ciprofloxacin, a fluorinated derivative of naladixic acid, has been available in the United States since late 1987. We have seen three patients who had seizures beginning shortly after starting ciprofloxacin therapy.  Report of Cases.—  Case1.—A 78-year-old man with a history of epilepsy since childhood had been seizure free for at least ten years. He had been taking phenytoin as his only medication. He was given ciprofloxacin, 500 mg every 12 hours, for a urinary tract infection. He had a grand mal epileptic seizure the next day. His phenytoin level was 19.8 μg/mL. Administration of ciprofloxicin was stopped. He has been seizure free for more than two months.  Case 2.—  A 64-year-old man had been on a stable regimen of medications, using indomethacin, prednisone, digoxin, glyburide, and allopurinol. To treat a urinary tract infection, he received cefazolin and gentamicin for five days. He changed to oral ciprofloxacin
Are routine breast and pelvic examinations necessary for women starting combined oral contraception?
Authors: A Scott, A F Glasier
Journal: Human Reproduction Update (2004)

Millions of women worldwide use combined oral contraception (COC). Most of them are in good health and have no contraindications to using any contraceptive method. Although extremely safe for the vast majority of women and even though the absolute risk of complications is very small, COC is associated with an increased relative risk of serious conditions including cardiovascular disease and breast and cervical cancer. In many countries, breast and pelvic examinations are routinely undertaken annually for all women using hormonal contraception. Breast and pelvic examination have low detection rates for abnormality and may yield clinically irrelevant results, causing anxiety and inconvenience to the patient for no obvious gain. There is no good evidence to support routine breast or pelvic examination either for women starting hormonal contraception or for monitoring long-term use.
Bias in Intervention Studies That Enroll Patients From High-Risk Clinics
Authors: Sholom Wacholder
Journal: JNCI Journal of the National Cancer Institute (2004)

It is important to evaluate the effects of proposed interventions to reduce the risk of disease among carriers of a highly penetrant mutation, such as the mutations in BRCA1 and BRCA2 for breast and ovarian cancers or in APC and MLH1 or MSH2 for colon cancer. However, some studies that evaluate the effects of interventions designed to reduce risk in mutation carriers may be susceptible to a serious selection bias when they are based in clinics that care for persons at high risk for the disease. A study design in which a large fraction of the case patients were diagnosed before being seen at the clinic and all control subjects are persons previously seen at the clinic can create a false impression of intervention efficacy if, as is likely, mutation carriers seen at the clinic were more likely to receive the intervention than mutation carriers in the general population.
CD40
Authors: Sreenivas Laxmanan, Dipak Datta, Christopher Geehan, David M Briscoe, Soumitro Pal
Journal: Journal of the American Society of Nephrology (2005)

Infiltration of immune cells into the renal interstitium is characteristic of chronic inflammatory kidney diseases. CD4+ T cells and platelets express CD40 ligand (CD40L) and are reported to mediate proinflammatory events in renal proximal tubular epithelial cells (RPTEC) via interaction with CD40. In other cell types, CD40 signals can also induce protective genes. Here, human RPTEC were treated with sCD40L to ligate CD40, and a significant increase in the generation of proinflammatory reactive oxygen species was found; however, CD40-activated cells did not undergo apoptosis. This suggests that CD40 signals may simultaneously induce antiapoptotic genes for cytoprotection of RPTEC. Heme oxygenase-1 (HO-1) expressed in RPTEC serves as a protective gene, but it is not known whether it is regulated by CD40. Next, RPTEC were transiently transfected with a full-length HO-1 promoter-luciferase construct and were treated with sCD40L. CD40 ligation was found to significantly increase HO-1 promoter activity. By electrophoretic mobility shift assay, it was confirmed that CD40 signaling induced the transcriptional activation of HO-1 through the binding of NF-kappaB to its promoter. By Western blot analysis, a marked increase in HO-1 protein expression following CD40 ligation was also found. These observations are of clinical significance because it was found that CD40 and HO-1 are induced in expression in vivo in inflamed rejecting kidney biopsies and co-expressed in renal tubules. Therefore, ligation of CD40 in RPTEC promotes both inflammatory and anti-inflammatory processes. Regulating the balance between these two events may be of importance in the prevention of tubular injury associated with renal disease.