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41.
Gloria Valdes Peter Kaufmann Jenny Corthorn Rafaela Erices K Bridget Brosnihan JaNae Joyner-Grantham 《Reproductive biology and endocrinology : RB&E》2009,7(1):79-20
We postulate that an orchestrated network composed of various vasodilatory systems participates in the systemic and local
hemodynamic adaptations in pregnancy. The temporal patterns of increase in the circulating and urinary levels of five vasodilator
factors/systems, prostacyclin, nitric oxide, kallikrein, angiotensin-(1–7) and VEGF, in normal pregnant women and animals,
as well as the changes observed in preeclamptic pregnancies support their functional role in maintaining normotension by opposing
the vasoconstrictor systems. In addition, the expression of these vasodilators in the different trophoblastic subtypes in
various species supports their role in the transformation of the uterine arteries. Moreover, their expression in the fetal
endothelium and in the syncytiotrophoblast in humans, rats and guinea-pigs, favour their participation in maintaining the
uteroplacental circulation. The findings that sustain the functional associations of the various vasodilators, and their participation
by endocrine, paracrine and autocrine regulation of the systemic and local vasoactive changes of pregnancy are abundant and
compelling. However, further elucidation of the role of the various players is hampered by methodological problems. Among
these difficulties is the complexity of the interactions between the different factors, the likelihood that experimental alterations
induced in one system may be compensated by the other players of the network, and the possibility that data obtained by manipulating
single factors in vitro or in animal studies may be difficult to translate to the human. In addition, the impossibility of
sampling the uteroplacental interface along normal pregnancy precludes obtaining longitudinal profiles of the various players.
Nevertheless, the possibility of improving maternal blood pressure regulation, trophoblast invasion and uteroplacental flow
by enhancing vasodilation (e.g. L-arginine, NO donors, VEGF transfection) deserves unravelling the intricate association of
vasoactive factors and the systemic and local adaptations to pregnancy. 相似文献
42.
Njajou OT Blackburn EH Pawlikowska L Mangino M Damcott CM Kwok PY Spector TD Newman AB Harris TB Cummings SR Cawthon RM Shuldiner AR Valdes AM Hsueh WC 《PloS one》2010,5(9):e13048
Background
Telomeres shorten as cells divide. This shortening is compensated by the enzyme telomerase. We evaluated the effect of common variants in the telomerase RNA component (TERC) gene on telomere length (TL) in the population-based Health Aging and Body Composition (Health ABC) Study and in two replication samples (the TwinsUK Study and the Amish Family Osteoporosis Study, AFOS).Methodology
Five variants were identified in the TERC region by sequence analysis and only one SNP was common (rs2293607, G/A). The frequency of the G allele was 0.26 and 0.07 in white and black, respectively. Testing for association between TL and rs2293607 was performed using linear regression models or variance component analysis conditioning on relatedness among subjects.Results
The adjusted mean TL was significantly shorter in 665 white carriers of the G allele compared to 887 non-carriers from the Health ABC Study (4.69±0.05 kbp vs. 4.86±0.04 kbp, measured by quantitative PCR, p = 0.005). This association was replicated in another white sample from the TwinsUK Study (6.90±0.03 kbp in 301 carriers compared to 7.06±0.03 kbp in 395 non-carriers, measured by Southern blots, p = 0.009). A similar pattern of association was observed in whites from the family-based AFOS and blacks from the Health ABC cohort, although not statistically significant, possibly due to the lower allele frequency in these populations. Combined analysis using 2,953 white subjects from 3 studies showed a significant association between TL and rs2293607 (β = −0.19±0.04 kbp, p = 0.001).Conclusion
Our study shows a significant association between a common variant in TERC and TL in humans, suggesting that TERC may play a role in telomere homeostasis. 相似文献43.
P McMaster A Procyshyn R Y Calne R Valdes K Rolles D J Smith 《BMJ (Clinical research ed.)》1980,280(6212):444-445
Studies were conducted on dogs to test the efficacy of cyclosporin A (CyA) in prolonging normoglycaemia and graft survival after whole-organ pancreas allograft transplantation. Five dogs subjected to pancreatectomy alone served as controls. Withholding immunosuppression after transplantation (five animals) resulted in the same median duration of survival as occurred in the controls (13 days). Azathioprine and steroids (seven animals) produced median durations of normoglycaemia and survival of 9 and 23 days respectively. Animals given CyA 18 mg/kg/day (five) and 25 mg/kg/day (10), however, showed median durations of normoglycaemia of 18 and 55 days (p less than 0.05 and p less than 0.02) respectively and median survival times of 36 and 85 days (NS and p less than 0.02). If CyA proved effective in controlling rejection of pancreas allografts in man it would offer unstable diabetics in renal failure a more hopeful outlook than conventional immunosuppression. 相似文献
44.
For many HLA-associated diseases, multiple alleles-- and, in some cases, multiple loci--have been suggested as the causative agents. The haplotype method for identifying disease-predisposing amino acids in a genetic region is a stratification analysis. We show that, for each haplotype combination containing all the amino acid sites involved in the disease process, the relative frequencies of amino acid variants at sites not involved in disease but in linkage disequilibrium with the disease-predisposing sites are expected to be the same in patients and controls. The haplotype method is robust to mode of inheritance and penetrance of the disease and can be used to determine unequivocally whether all amino acid sites involved in the disease have not been identified. Using a resampling technique, we developed a statistical test that takes account of the nonindependence of the sites sampled. Further, when multiple sites in the genetic region are involved in disease, the test statistic gives a closer fit to the null expectation when some--compared with none--of the true predisposing factors are included in the haplotype analysis. Although the haplotype method cannot distinguish between very highly correlated sites in one population, ethnic comparisons may help identify the true predisposing factors. The haplotype method was applied to insulin-dependent diabetes mellitus (IDDM) HLA class II DQA1-DQB1 data from Caucasian, African, and Japanese populations. Our results indicate that the combination DQA1#52 (Arg predisposing) DQB1#57 (Asp protective), which has been proposed as an important IDDM agent, does not include all the predisposing elements. With rheumatoid arthritis HLA class II DRB1 data, the results were consistent with the shared-epitope hypothesis. 相似文献
45.
Effect of Ischemia on the In Vivo Release of Striatal Dopamine, Glutamate, and γ-Aminobutyric Acid Studied by Intracerebral Microdialysis 总被引:27,自引:16,他引:11
Mordecai Y.-T. Globus Raul Busto W. Dalton Dietrich Elena Martinez Isabel Valdes Myron D. Ginsberg 《Journal of neurochemistry》1988,51(5):1455-1464
We have previously described a marked attenuation of postischemic striatal neuronal death by prior substantia nigra (SN) lesioning. The present study was carried out to evaluate whether the protective effect of the lesion involves changes in the degree of local cerebral blood flow (ICBF) reduction, energy metabolite depletion, or alterations in the extracellular release of striatal dopamine (DA), glutamate (Glu), or gamma-aminobutyric acid (GABA). Control and SN-lesioned rats were subjected to 20 min of forebrain ischemia by four-vessel occlusion combined with systemic hypotension. Levels of ICBF, as measured by the autoradiographic method, and energy metabolites were uniformly reduced in both the ipsi- and contralateral striata at the end of the ischemic period, a finding implying that the lesion did not affect the severity of the ischemic insult itself. Extracellular neurotransmitter levels were measured by microdialysis; the perfusate was collected before, during, and after ischemia. An approximately 500-fold increase in DA content, a 7-fold increase in Glu content, and a 5-fold increase in GABA content were observed during ischemia in nonlesioned animals. These levels gradually returned to baseline by 30 min of reperfusion. In SN-lesioned rats, the release of DA was completely prevented, the release of GABA was not affected, and the release of Glu was partially attenuated. However, excessive extracellular Glu concentrations were still attained, which are potentially toxic. This, taken together with the previous neuropathological findings, suggests that excessive release of DA is important for the development of ischemic cell damage in the striatum. 相似文献
46.
A Valdivia M Marrero M Alvarez M Mune O Valdes G Roges 《Memórias do Instituto Oswaldo Cruz》1992,87(1):99-102
Immunofluorescence and immunoperoxidase test directed against early viral antigens, and DNA-DNA hybridization were compared with viral isolation for their abilities to detect Cytomegalovirus (CMV) in the urine of 89 HIV infected patients. From the 100 urine samples collected, 70 were found positive by at least one method. Considering viral isolation as the "gold standard" technique, immunofluorescence and immunoperoxidase had a sensitivity of 92.3% and 88% respectively, with a specificity in both cases of 95%. DNA-DNA hybridization showed a sensitivity of 90% but with lower (60%) specificity. All of the three assays were effective in detecting CMV from urine and the technical advantage of each is discussed. 相似文献
47.
Giusi Barbata Laura Valdes Giuseppe Sermonti 《Molecular & general genetics : MGG》1973,126(3):227-232
Summary In heterokaryons between pairs of aconidial mutants of Aspergillus nidulans one of the component strains usually shows a striking prevalance in the contribution to the conidial crop. By assuming that the prevailing strain is blocked earlier and the succumbent one later in the process of differentiation, a series of mutations can be arranged in a consistent order.Some mutant strains do not fit the scheme exactly but show a general tendency to be succumbent to early mutants and prevalent over the late ones. A criterion for arraying genes involved in differentiation according to the order of their physiological action is proposed. 相似文献
48.
Nabil A. Mansour James J. Valdes Adil E. Shamoo Zoltan Annau 《Journal of biochemical and molecular toxicology》1987,2(1):25-42
Purified Torpedo nobiliana electric organ acetylcholine receptor (AChR) was reconstituted into membranes containing natural phospholipids supplemented with cholesterol (25% w/w). The reconstituted system facilitates the study of the effects of drugs on the regulation of the AChR channel complex under both resting and carbachol (carb)-stimulated conditions. Neostigmine (Neo) was the only carbamate to induce activation of [3-H]-phencyclidine ([3-H]-PCP) binding to the channel sites, acting as a weak agonist. The activation of [3-H]-PCP binding is dependent upon the nature of the reconstituted systems, with carb/Neo activation ratios of 8, 3, and 1 for the intact purified AChR vesicles fraction (PVF), the PVF reconstituted in phospholipid/cholesterol (CRPVF), and the PVF reconstituted in phospholipid (RPVF), respectively. The carbamates Neo, physostigmine (Physo), and pyridostigmine (Pyrido) inhibited carb-activated [3-H]-PCP binding with Ki values of 10, 20, and 1,600 μM, respectively. The inhibition was mixed competitivenoncompetitive in nature. The characteristic response of CRPVF to carb-stimulated [22-Na] influx was inhibited by the three carbamates, with IC-50 values of 6,50, and 1,000 μM for Neo, Physo, and Pyrido, respectively. The quaternary ammonium organophosphate ecothiophate (Eco) inhibited carb-stimulated [22-Na] influx with potency similar to that of Neo. Preincubation of AChR preparation with the carbamates and ecothiophate caused a reduction in the binding of [125-I]-α- bungarotoxin ([125-I]-α-BGT) with the following decreasing order of potency: Neo < Physo < Eco < Pyrido. Calcium has a direct modulatory role on the time-course inhibition of [125-I]-α-BGT binding by these drugs. While we observed a high potency of Neo and Physo in inhibiting [125-I]-α-BGT binding, it was undetectable for the carbamate insecticide 2-methyl-2-(methylthio)propionaldehyde-O-(methylcarbamoyl)oxime (aldicarb). These data suggest that the potent anticholinesterase carbamate agents interact differently with the AChR and its ionic channel. Their interactions with the nicotinic AChR channel system can be described as (a) weakly agonist, (b) directly acting on the open conformation of the channel, and (c) blocking the AChR-binding sites. 相似文献
49.
J L Bermudez J P Chambers E Rizopoulos P Kumar J J Valdes A O Martinez 《Cell calcium》1989,10(4):181-187
The Ca2+-stimulated, Mg2+-dependent ATPase of SV40 transformed WI38 lung fibroblast homogenates exhibits a high affinity for Ca2+ (K0.5 = 0.20 microM) and moderately high affinity for ATP (Km = 28.6 microM) and Mg2+ (K0.5 = 138.5 microM). This activity was NaN3, KCN and oligomycin insensitive but very sensitive to vanadate (I50 = 0.5 microM) suggesting its being neither mitochondrial or microsomal but plasma membrane in origin. Under optimal conditions of protein, hydrogen ion and substrate concentration, 16-19 nmoles phosphate was released per min per mg protein. Hill plot analysis indicated no cooperativity to occur between Ca2+ binding sites. Nucleotides other than ATP and dATP were ineffective as substrates. The trivalent cation, lanthanum (La3+) completely inhibited hydrolysis of ATP at approximately 70 microM (I50 = 25 microM). Calmodulin antagonists trifluoperazine and calmidazolium inhibited ATP hydrolysis in a dose dependent fashion. 相似文献
50.
Hsuan‐Chen Wu Xiao‐Wen Shi Chen‐Yu Tsao Angela T. Lewandowski Rohan Fernandes Chi‐Wei Hung Philip DeShong Eiry Kobatake James J. Valdes Gregory F. Payne William E. Bentley 《Biotechnology and bioengineering》2009,103(2):231-240
We report the assembly of seven different antibodies (and two antigens) into functional supramolecular structures that are specifically designed to facilitate integration into devices using entirely biologically based bottom‐up fabrication. This is enabled by the creation of an engineered IgG‐binding domain (HG3T) with an N‐terminal hexahistidine tag that facilitates purification and a C‐terminal enzyme‐activatable pentatyrosine “pro‐tag” that facilitates covalent coupling to the pH stimuli‐responsive polysaccharide, chitosan. Because we confer pH‐stimuli responsiveness to the IgG‐binding domain, it can be electrodeposited or otherwise assembled into many configurations. Importantly, we demonstrate the loading of both HG3T and antibodies can be achieved in a linear fashion so that quantitative assessment of antibodies and antigens is feasible. Our demonstration formats include: conventional multiwell plates, micropatterned electrodes, and fiber networks. We believe biologically based fabrication (i.e., biofabrication) provides bottom‐up hierarchical assembly of a variety of nanoscale components for applications that range from point‐of‐care diagnostics to smart fabrics. Biotechnol. Bioeng. 2009;103: 231–240. © 2008 Wiley Periodicals, Inc. 相似文献