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Biomedical subjects

Ana M Sanchez

Publications and source records attributed to Ana M Sanchez.

7 recordsLinked to original sources

Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue.

Vanilloid receptor subtype-1 (TRPV1), the founding member of the vanilloid receptor-like transient receptor potential channel family, is a non-selective cation channel that responds to noxious stimuli such as low pH, painful heat and irritants. In the present study, we show, as means of reverse transcriptase-polymerase chain reaction and Western blot analysis, that the vanilloid TRPV1 receptor is expressed in the prostate epithelial cell lines PC-3 and LNCaP as well as in human prostate tissue. The kinetic parameters inferred from [(125)I]-resiniferatoxin binding were in concordance with data of TRPV1 receptors expressed in other tissues. The contribution of the endogenously expressed TRPV1 channel to intracellular calcium concentration increase in the prostate cells was studied by measuring changes in Fura-2 fluorescence by fluorescence microscopy. Addition of capsaicin, (R)-methanandamide and resiniferatoxin to prostate cells induced a dose-dependent increase in the intracellular calcium concentration that was reversed by the vanilloid TRPV1 receptor antagonist capsazepine. These results indicate that the vanilloid TRPV1 receptor is expressed and functionally active in human prostate cells.

Arachidonic Acids↗

The impact of male-to-male sexual experience on risk profiles of blood donors.

BACKGROUND: Men who have had sex with men (MSM) since 1977 are permanently deferred from donating blood. Excluding only men who engaged in male-to-male sex within either the prior 12 months or 5 years has been proposed. Little is known about infectious disease risks of MSM who donate blood. STUDY DESIGN AND METHODS: Weighted analyses of data from an anonymous mail survey of blood donors were conducted to examine the characteristics of men reporting male-to-male sex during specified time periods. RESULTS: Of the 25,168 male respondents, 569 (2.4%) reported male-to-male sex, 280 (1.2%) since 1977. Compared to donors who did not report male-to-male sex, the prevalence of reactive screening test results was higher among donors who reported the practice within the past 5 years (< or =12 months odds ratio [OR] 5.3, 95% confidence interval [CI] 2.6-10.4; >12 months to 5 years, OR 7.1, 95% CI 1.2-41.7); however, no significant difference was found for donors who last practiced male-to-male sex more than 5 years ago (>5 years-after 1977, OR 1.4, 95% CI 0.7-2.6; 1977 or earlier, OR 1.6, 95% CI 0.7-3.7). The prevalence of unreported deferrable risks (UDRs) other than male-to-male sex was significantly higher for all donors who reported male-to-male sex with ORs ranging from 3.1 to 18.9 (p < or = 0.01). CONCLUSIONS: No evidence was found to support changing current policy to permit donations from men who practiced male-to-male sex within the past 5 years. For donors with a more remote history of male-to-male sex, the findings were equivocal. A better understanding of the association between male-to-male sex and other UDRs appears needed.

Blood Banks↗

Mammalian brain consumption by blood donors in the United States: brains today, deferred tomorrow?

BACKGROUND: Theoretical concerns of possible variant CJD (vCJD) transmission by transfusion have led to deferral of US donors potentially exposed to the bovine spongiform encephalopathy agent. Although the efficacy of these policies is unknown, impact on blood collections has been substantial. Under the precautionary principle, deferral of donors consuming bovine (or other mam-malian) brains, possibly contaminated with the vCJD agent, might be considered. Blood donors were surveyed to determine lifetime mammalian brain consumption. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study (REDS) conducted an anonymous mail survey of 92,581 donors from eight US blood centers. RESULTS: Responses were received from 52,650 donors (57%). Of these, 6.4 percent reported lifetime brain consumption; bovine (3.6%) and hog brains (1.7%) were the most common. Bovine brain consumption varied fourfold by center (1.7-7.0%) and was highest among male (4.5%), older (age 55+, 6.5%), foreign-born (9.2%), Asian (7.2%), and Hispanic (8.6%) donors. Among bovine brain consumers, 67 percent engaged in the practice 4 times or less, 79 percent were repeat donors, and 61 percent reported giving at least 11 donations in the past 10 years. CONCLUSION: Following the precautionary principle, further steps to reduce the theoretical vCJD risk could include deferring donors who eat bovine (or other mammalian) brains. The impact of such a policy would not be trivial, especially in areas with older, foreign-born, Asian, or Hispanic donors. Cautious implementation and periodic evaluation of deferral policies is warranted.

Adolescent↗

Initiation of repair of A/G mismatches is modulated by sequence context.

The efficiency of DNA glycosylases to initiate base excision repair (BER) has been demonstrated to be modulated by the precise sequence context in which the lesion or mismatch is located. In the case of DNA containing an A/G mismatch, in which the recognition and excision of adenine from the mismatch is mediated by the Escherichia coli MutY enzyme, not only does the local sequence context affect the strength of base stacking interactions, but it also modulates the syn/anti conformation around the glycosyl bond of the bases in the mispair. Utilizing prior NMR data to identify DNA sequence contexts that adopt either an anti/anti or a syn/anti configuration at an A/G mismatch, we tested the hypothesis that the initial equilibrium of the mismatched base orientations would modulate the overall efficiency of glycosyl bond scission. By systematically varying the sequence context around a central A/G mismatch within a 30-mer duplex DNA, significant kinetic differences were observed that were consistent with this hypothesis. Since the relative efficiency of the kinetics fell into only two groupings, a NMR study was conducted on a DNA sequence context of unknown syn/anti conformation. These data established that the relative syn/anti conformation did not correlate with the excision efficiency, as well as there being a lack of correlation between kinetics and thermal stability of these DNAs.

Base Pair Mismatch↗

Comparative evaluation of the bioreactivity and mutagenic spectra of acrolein-derived alpha-HOPdG and gamma-HOPdG regioisomeric deoxyguanosine adducts.

Acrolein is a bifunctional electrophile, present as an ubiquitous environmental pollutant and an endogenous cellular product of lipid peroxidation. Reaction of acrolein with deoxyguanosine produces two regioisomeric DNA adducts, specifically gamma-hydroxypropanodeoxyguanosine (gamma-HOPdG) and alpha-hydroxypropanodeoxyguanosine (alpha-HOPdG). While previous investigations have focused on the major gamma-HOPdG adduct, little is known about the properties of the minor alpha-HOPdG adduct. Therefore, this comparative investigation has assessed the following: the ability of each adduct to undergo secondary chemical reactions with biomolecules to form various cross-linked species, in vitro translesion DNA synthesis, and mutagenic properties, following replication in mammalian cells. In contrast to gamma-HOPdG, which is capable of forming DNA-DNA, DNA-peptide, and DNA-protein cross-links, alpha-HOPdG did not form any of these cross-linked species. These results can be attributed to the inability of the alpha-HOPdG adduct to undergo ring opening, whereas the gamma-HOPdG adduct forms the ring open, acyclic N(2) oxopropyl in duplex DNA, which readily reacts with nucleophilic functions. Consistent with this interpretation, when polymerase eta replication bypass of DNA containing alpha-HOPdG was assayed, this lesion posed a stronger block to replication than the gamma-HOPdG adduct, closely resembling the results for polymerase eta bypass of propanodeoxyguanosine in which the exocyclic adduct remains permanently ring-closed. Cellular replication and mutagenesis assays in COS-7 cells using single-stranded DNA containing a site specific alpha-HOPdG revealed that this adduct was significantly mutagenic, yielding a nearly identical frequency and spectrum of mutations as compared with the gamma-HOPdG adduct.

Acrolein↗

Blood-donor perceptions of health history screening with a computer-assisted self-administered interview.

BACKGROUND: Computer-assisted self-interviewing (CASI) has been shown to promote disclosures of sensitive information. Using CASI to screen blood-donor candidates might encourage reports of deferrable risks without discouraging eligible donors. STUDY DESIGN AND METHODS: In 1998, an anonymous mail survey was sent to donors from eight blood centers. The relationship of donor demographics, donation history, and infectious risks (HIV test-seeking behavior, unreported deferrable risk, or reactive donor-screening test result) on attitudes toward CASI were assessed. RESULTS: Of 92,581 blood donors surveyed, 52,650 (57%) responded; of these, 4713 (7%) had an infectious risk. Among donors with risks, 29 percent felt they would be encouraged to reveal personal data, and 7 percent reported they would be discouraged from donating by CASI. Young, minority, female, and first-time donors were the most likely to report that CASI would encourage personal disclosures. Among donors without risks, 5 percent felt CASI would discourage them from donating. CONCLUSIONS: Although most donors felt their donation practices would not be influenced, CASI might reduce the proportion of donors with infectious risks by fostering personal disclosures and self-deferrals. The potential for CASI to improve donor screening and increase appropriate self-deferrals should be balanced against the possible loss of reluctant safe donors.

Adolescent↗

Increasing blood availability by changing donation patterns.

BACKGROUND: There is a declining margin between US blood collections and transfusions. Donation patterns were examined to characterize returning first-time donors and predict the impact on blood availability of decreasing the number of nonreturning donors. STUDY DESIGN AND METHODS: First-time donors giving between 1991 and 1994 were followed for 3 to 6 years. The impact of decreasing the number of nonreturning donors in a 12-month period was projected using the Poisson distribution to model the donation patterns of 539,063 donors who gave in 1995. Repeat donors were classified as "returning first-time" (gave a first-time donation within 12 months of their index donation), "established" (gave a repeat donation), and "inactive" (didn't donate in the 12 months before their index donation). RESULTS: A total of 49 percent of first-time donors did not return within 6 years. Returning first-time donors tended to be US born, white, and had more than a high school education. In 1995, 30 percent of donors were first time, 31 percent were established, 7 percent were returning first time, and 32 percent were inactive, giving 1.5, 2.4, 1.9, and 1.7 donations in 12 months, respectively. Reducing nonreturning donors by 5 percent could increase blood collections by 2.7 percent. Similarly, 15 or 25 percent reductions in nonreturns could increase collections by 8.6 or 16.0 percent, respectively. CONCLUSIONS: Most donors are not giving near the donation limit. A substantial increase in donations could be achieved by a relatively small decrease in donor nonreturn. Research is needed to understand why approximately half of first-time donors donate only once.

Behavior↗