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X Gao

Publications and source records attributed to X Gao.

At least 73 records · Page 4Linked to original sources
PubMed2001

Novel methylation targets in de novo acute myeloid leukemia with prevalence of chromosome 11 loci.

Aberrant DNA methylation is believed to be important in tumorigenesis by causing either transcriptional inactivation of genes or chromosomal instability. Several laboratories have identified promoter hypermethylation of tumor suppressor genes in acute myeloid leukemia (AML). However, these studies do not provide a global assessment of overall methylation changes and do not allow the identification of novel methylated sequences. Previously, nonrandom CpG island methylation was reported in 17 adult de novo AML diagnostic samples when compared with the corresponding remission samples by means of restriction landmark genomic scanning (RLGS). That study has been expanded on by an analysis of a larger set of CpG islands (1740 vs 1184), which now provides details of 33 cloned methylated loci, including 21 known genes or expressed sequence tags. Five of these cloned loci appear to be methylated only in AML and not in the 6 solid tumors studied in this study (more than 98 samples analyzed). Chromosomal location was available for 30 of the 33 loci, and 5 of these 30 (17%) are localized to chromosome 11, suggesting a trend toward overrepresentation of methylation events on this chromosome. These results provide evidence for widespread aberrant methylation in AML, with identification of novel methylation targets, epigenetic changes that appear unique to AML, and apparent preferential methylation on chromosome 11.

Adult↗
PubMed2001

Expression of 5-HT2A receptor mRNA in rat spinal dorsal horn and some nuclei of brainstem after peripheral inflammation.

The expression of 5-hydroxytryptamine 5-HT2A receptor mRNA was studied in the lumbar spinal dorsal horn, nucleus of raphe magnus (NRM), ventrolateral periaqueductal gray (vlPAG) and dorsal raphe nucleus (DRN) following carrageenan inflammation using in situ hybridization technique. The findings of this study demonstrated that 5-HT2A receptor mRNA was expressed with low to moderate levels in lumbar spinal dorsal horn, NRM, vlPAG and DRN. Following carrageenan inflammation, the expression of 5-HT2A receptor mRNA in ipsilateral dorsal horn, bilateral NRM, vlPAG and DRN was significantly increased. The peak occurred at 3 h and then there was a clear decrease but still a substantial number of labeled cells at 24 h after injection of carrageenan. This result suggested that the synthesis of 5-HT2A receptor is enhanced in spinal dorsal horn, NRM, vlPAG and DRN during inflammatory pain.

Animals↗
PubMed2001

Effects of dopaminergic agents on carrageenan hyperalgesia after intrathecal administration to rats.

The present study explored the role of dopaminergic transmission in spinal cord in a model of carrageenan-induced inflammatory pain by examining the effects of selective agonists and antagonists of dopamine receptors. The results were as follows: (1) trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g] quinoline hydrochloride (LY171555), a dopamine D(2) receptor agonist, produced anti-hyperalgesia (150 and 300 nmol) or hypoalgesia (300 nmol) in the inflamed hindpaws and non-inflamed hindpaws, respectively; spiperone hydrochloride (8-[4-(4-fluorophenyl)-4-oxobutyl]-1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one hydrochloride), a dopamine D(2) receptor antagonist, decreased the pain threshold of non-inflamed hindpaws (300 nmol). (2) (+/-)-SKF38393 hydrochloride ((+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride), a dopamine D(1) receptor agonist, had no effect on either hindpaw, even at a higher dose (300 nmol); R(+)-7-Chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (R(+)-SCH23390 hydrochloride), a dopamine D(1) receptor antagonist, induced anti-hyperalgesia in the inflamed hindpaws (300 nmol). The present results suggest that the dopaminergic system in the spinal cord is involved in the central modulation of inflammatory hyperalgesia, and that the different effects are probably induced by different receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2001

Transformation of sib-pair values for the Haseman-Elston method.

The squared sib-pair phenotype difference (SQD) has been used as a dependent variable in the Haseman-Elston (H-E) regression quantitative-trait locus (QTL) linkage method, but it has been shown that the SQD does not make full use of linkage information. In this study, we examine the efficiency of SQD in H-E regression compared to other proposed functions of the sib-pair phenotypes. A new function of sib-pair phenotypes, the product of pair values corrected with family mean (PCF), is shown to have desirable properties in many realistic situations. Consistent results were obtained using a combination of large-sample analytic approximations, simulation, and analyses of quantitative-trait data from Genetic Analysis Workshop 10. The advantages of PCF are further improved in the presence of family-specific effects arising from environmental factors or when additional QTLs influence the trait. All of the phenotype functions are incorporated in our new, freely available linkage-mapping program MULTIGENE 1.0 for the PC environment.

Chromosome Mapping↗
PubMed2001

PEGylated PLGA nanoparticles as protein carriers: synthesis, preparation and biodistribution in rats.

The aim of the present work was to assess the merits of PEGylated poly(lactic-co-glycolic acid) (PEG-PLGA) nanoparticles as protein and peptide drugs (PPD) carriers. PEG-PLGA copolymer, which could be used to prepare the stealth nanoparticles or long-circulating nanoparticles, was synthesized with methoxypolyethyleneglycol (MePEG) and PLGA. The structure of PEG-PLGA was confirmed with (1)H NMR and Fourier transform infrared (FTIR) spectrum, and molecular weight was determined by gel permeation chromatography (GPC). Bovine serum albumin (BSA), chosen as model protein, was encapsulated within the stealth nanoparticles with the double emulsion method. The particles were characterized in terms of size, zeta potential and in vitro release of the protein. The biological fate of the BSA-loaded nanoparticles following intravenous administration was determined over 24 h in rats. The experimental results showed that PEG-PLGA could be obtained by ring-opening polymerization of lactide and glycolide in the presence of MePEG. (1)H NMR and FTIR spectrum were consistent with the structure of PEG-PLGA copolymer. Molecular weight determined by GPC was 50800. The stealth nanoparticles loading BSA could be prepared by the double emulsion technique. The entrapment efficiency was 48.6%, particle size about 200 nm and zeta potential -16.1 mV. BSA release from the stealth nanoparticles showed an initial burst release and then sustained release. PEG-PLGA nanoparticles could extend half-life of BSA from 13.6 min of loaded in PLGA nanoparticles to 4.5 h and obviously change the protein biodistribution in rats compared with that of PLGA nanoparticles. Thus, PEG-PLGA nanoparticles could be an effective carrier for PPD delivery.

Animals↗
PubMed2001

Effects of intraplantar injection of carrageenan on central dopamine release.

The present study examined the changes of extracellular concentration of dopamine and its metabolite homovanillic acid in the striatum, the periaqueductal gray and the dorsal horn of lumbar spinal cord following intraplantar injection of carrageenan. In vivo microdialysis and high-performance liquid chromatography with electrochemical detection were performed. The results showed that intraplantar injection of carrageenan significantly increased dopamine or homovanillic acid levels in the different central regions. The present study suggested that the central dopamine system (at least including ascending nigrostrialtal pathway and descending A11--the dorsal horn fibers) be activated following the carrageenan, while the activation probably mediated antinociception.

Animals↗
PubMed2001

The effect of testosterone upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system.

The gonadal steroid hormone estrogen (E) can function as a neuroprotectant of nigrostriatal dopaminergic (NSDA) neurotoxicity, however, there exists very limited information on the role of testosterone (T) in this capacity. In the present report, the effects of T on methamphetamine (MA) induced neurotoxicity of the NSDA system were examined in gonadectomized female and male CD-1 mice. In Experiment 1, striatal dopamine (DA) concentrations and output from T-treated ovariectomized mice were not significantly different from that of non-T-treated mice following MA. These results suggest that T is not functioning as a modulator of MA-induced NSDA neurotoxicity in ovariectomized CD-1 mice. In Experiment 2, there were no significant differences in DA concentrations or output among T-treated, non-T-treated as well as E-treated orchidectomized mice following MA. The results of Experiment 2 indicate that the neuroprotective effect of E reported within ovariectomized mice is not seen in male mice. Nor does T appear to function as a modulator of MA neurotoxicity in male mice. These effects of T and E upon the MA induced neurotoxicity of the NSDA system have important implications for the gender differences which are observed in animal models of NSDA neurotoxicity and in Parkinson's disease.

Animals↗
PubMed2001

MSH6 and MSH3 are rarely involved in genetic predisposition to nonpolypotic colon cancer.

A set of 90 nonpolypotic colon cancer families in which germ-line mutations of MSH2 and MLH1 had been excluded were screened for mutations in two additional DNA mismatch repair genes, MSH6 and MSH3. Kindreds fulfilling and not fulfilling the Amsterdam I criteria, showing early and late onset colorectal (and other) cancers, and having microsatellite stable and unstable tumors were included. Two partly parallel approaches were used: genetic linkage analysis (19 large families) and the protein truncation test (85, mostly smaller, families). Whereas MSH3 was not involved in any family, a large Amsterdam-positive, late-onset family showed a novel germ-line mutation in MSH6 (deletion of CT at nucleotide 3052 in exon 4). The mutation was identified through genetic linkage (multipoint lod score 2.4) and subsequent sequencing of MSH6. Furthermore, the entire MSH6 gene was sequenced exon by exon in families with frameshift mutations in the (C)8 tract in tumors, previously suggested as a predictor of MSH6 germ-line mutations; no mutations were found. We conclude that germ-line involvement of MSH6 and MSH3 is rare and that other genes are likely to account for a majority of MSH2-, MLH1-mutation negative families with nonpolypotic colon cancer.

Adult↗
PubMed2001

A review of mechanisms controlling ovulation with implications for the anovulatory effects of polychlorinated dibenzo-p-dioxins in rodents.

Polychlorinated dibenzo-p-dioxins (PCDDs) can impinge on female fertility by preventing ovulation. In this review, the aspects of normal ovulatory physiology most relevant to our current understanding of PCDD action on the ovary are briefly reviewed. This is followed by a comprehensive assessment of data relevant to the effects of PCDDs during ovulation in the rat. PCDDs interrupt ovulation through direct effects on the ovary in combination with dysfunction of the hypothalamo-hypophyseal axis.

Animals↗
PubMed2001

2,3,7,8-tetrachlorodibenzo-p-dioxin decreases responsiveness of the hypothalamus to estradiol as a feedback inducer of preovulatory gonadotropin secretion in the immature gonadotropin-primed rat.

Sprague-Dawley rats (23-day-old) were dosed with TCDD (32 microg/kg) in corn oil or vehicle alone. Equine chorionic gonadotropin (eCG) was injected (5 IU, sc) 24 h later to induce follicular development. Another 24 h later, half of TCDD- or corn oil-treated rats were injected (sc) with 17 beta-estradiol-cypionate (ECP, at 0.004 to 0.5 mg/kg). Blood and ovaries were collected on expected proestrous (preovulatory period) at 51, 54, and 58 h after eCG injection as well as in the morning after ovulation (72 h after eCG). Serum concentrations of 17 beta-estradiol (E), progesterone (P), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined by radioimmunoassay. The number of ova shed was measured at 72 h after injection of eCG by irrigating ova from oviducts. During the preovulatory period (approximately 58 h after eCG injection), a circulating level of 70-100 pg E/ml coincided with LH and FSH surges and later normal ovulation of 10 to 12 ova/rat was observed in controls. However, the same concentration of E was not associated with LH and FSH surges in rats treated with TCDD (32 microg/kg), resulting in reduced ovarian weight gain and reduction of ovulation by 70 to 80% (2-3 ova/rat). Blockage of the gonadotropin surge, reduced ovarian weight gain, and ovulation were all reversed completely by the lowest effective dose of ECP (0.1 mg/kg). At 72 h after eCG, serum P secretion was reduced and serum E levels were significantly increased compared to those of corn oil-treated controls. ECP alone had no effect on serum P levels at any time point, but in rats treated with TCDD and ECP, both the reduction of P (at 58 and 72 h) and the increase in E secretion (72 h) were completely reversed. Further studies confirmed that restoration by ECP of gonadotropin surges and associated ovulation could not be attained until circulating levels of E rose sufficiently high to trigger the LH and FSH surges. The new action threshold of E for inducing gonadotropin surges in rats treated with TCDD (32 microg/kg) was determined to be eight- to 10-fold higher than that in controls. Thus, it is apparent that TCDD decreased the responsiveness of the hypothalamus to E as a feedback inducer of preovulatory gonadotropin secretion.

Animals↗
PubMed2001

NMR studies of adrenocorticotropin hormone peptides in sodium dodecylsulfate and dodecylphosphocholine micelles: proline isomerism and interactions of the peptides with micelles.

Three adrenocorticotropin hormone (ACTH) fragments (1-10, 1-24, and 11-24) have been studied in water and in sodium dodecylsulfate (SDS) and dodecylphosphocholine (DPC) micelles by nuclear magnetic resonance spectroscopy. The trans-cis isomerism at all three proline sites (at positions 12, 19, and 24) was found in the 11-24 segment of the peptide. The population of the cis isomers changes with the environment of the peptide. Specifically, the presence of the DPC micelle does not affect the trans-cis equilibrium in the 11-24 segment from that in water. In contrast, the presence of the SDS micelles decreases the population of the cis isomer at Pro(24), but increases its population at Pro(12) and Pro(19). The effect of SDS micelles on the trans-cis equilibrium at these proline sites was discussed. Intermolecular nuclear Overhauser effect (NOE) correlations between the ACTH peptides and the micelles were observed. These correlations occurred only in the 1-10 segment of the peptides, and the hydrophobic side chains contributed most to the intermolecular NOE. The intermolecular NOE pattern corroborates the suggestion that the 1-10 segment of the ACTH peptides bind to these micelles via a surface-binding mode, with most of the interactions coming from the insertion of the hydrophobic side chains.

Adrenocorticotropic Hormone↗
PubMed2001

Molecular dynamics simulation of adrenocorticotropin (1-10) peptide in a solvated dodecylphosphocholine micelle.

Adrenocorticotropin (ACTH) (1-10), an adrenocorticotropin hormone fragment, has been studied by molecular dynamics (MD) simulation in an NPT ensemble in an explicit dodecylphosphocholine (DPC) micelle. Two starting configurations of the peptide/micelle system, corresponding to the insertion and surface-binding modes, were used. A common equilibrated configuration, in which the peptide lies parallel to the micellar surface, was reached from both simulations. In the initial part of the simulations, distance restraints derived from NMR nuclear Overhauser enhancements were incorporated before the peptide reached an equilibrium configuration with respect to the micelle. Analyses of the trajectories from the subsequent free (unrestrained) MD simulation showed that ACTH (1-10) does not conform strictly to a helical structure. The loss of the helical structure is due to decreased intramolecular hydrogen bonding accompanied by an increase of hydrogen bonding between the amide protons of the peptide and the micellar head groups. However, the extent of the latter interaction is less pronounced than in the negatively charged SDS micelle. The final structure enhances the amphipathic nature of the peptide, facilitating better interactions at the water-hydrophobic interface. The primary hydrophobic interactions with the micelle came from the side chains of Met4, Phe7, and Trp9. All peptide bonds were either hydrated or were involved in intramolecular hydrogen bonding. The interactions with the DPC micelle, the conformation of the bound peptide, and the dynamics of the peptide, as revealed by the time correlation functions of the N-H bonds, were compared with those of the ACTH (1-10)/SDS system studied previously by MD simulations.

Adrenocorticotropic Hormone↗
PubMed2001

IL-12 gene therapy of leukemia with hematopoietic progenitor cells without the toxicity of systemic IL-12 treatment.

We have previously shown that the myeloid progenitor cell line 32Dc13 transduced with mIL-12 cDNAs (32DIL-12 cells) induces IFN-gamma and NK-cell-mediated cytotoxicity in vivo. Since systemic therapy with recombinant IL-12 protein has been shown to produce moderate to severe toxic side effects we examined whether IL-12 gene therapy with hematopoietic progenitor cells also induces systemic toxicities that are commonly associated with the administration of rIL-12 protein. Injection of large doses of IL-12 secreting 32DIL-12 cells (5 to 6 x 10(7) cells) significantly reduced mortality in mice injected with a lethal dose of 32Dp210 myeloid leukemia cells. More importantly, injection of similar doses of transduced cells failed to reduce body weight significantly or produce other visible signs of toxicity, i.e., fur ruffling or lethargy. There was no evidence of hematologic or hematopoietic toxicity resulting from the injection of transduced cells. In addition, microscopic examination of liver, kidney, lung, and intestine of mice injected with transduced cells revealed the absence of tissue necrosis or inflammatory response in any of these organs. Finally, 32DIL-12 cells were not found to interfere with the engraftment of syngeneic bone marrow transplant or the hematopoietic reconstitution of irradiated mice. These results demonstrate that IL-12 gene therapy with hematopoietic progenitor cells is nontoxic and provide a rationale for exploring the feasibility of treating minimal residual leukemia with IL-12 gene therapy.

Animals↗
PubMed2001

Evaluation of nigrostriatal dopaminergic function in adult +/+ and +/- BDNF mutant mice.

Deletion of a single copy of the BDNF gene has been shown to affect the nigrostriatal dopaminergic system of young adult BDNF mice. In the present report we evaluated various indices of nigrostriatal dopaminergic function between 9-month-old wild-type (+/+) and heterozygous (+/-) BDNF mutant mice. Performance in a sensorimotor beam walking task was significantly decreased in +/- mice as indicated by increased times required to traverse both a wide (21 mm) and narrow (6 mm) beam. No differences in spontaneous locomotor behavior were observed between the +/+ and +/- mice. Amphetamine-stimulated (5 mg/kg) locomotor behavior was increased to a greater degree in the +/- mice, with the number of movements performed by these mice being significantly greater than their +/+ controls. Corpus striatal dopamine concentrations were significantly greater in the +/- BDNF mice. The absence of any significant differences for dopamine concentrations within the hypothalamus and olfactory bulb of these mice, as well as an absence of any difference in striatal norepinephrine concentrations, suggested a relative specificity of these effects to the corpus striatum. Both the +/- and +/+ mice showed similar reductions in striatal dopamine concentrations in response to a neurotoxic regimen of methamphetamine (20 mg/kg). Collectively these data show increased levels of striatal dopamine concentrations associated with altered behavioral responses involving the nigrostriatal dopaminergic system within the heterozygous BDNF mutant mice.

Animals↗
PubMed2001

Opposite association of two PPARG variants with cancer: overrepresentation of H449H in endometrial carcinoma cases and underrepresentation of P12A in renal cell carcinoma cases.

Peroxisome proliferator activated receptor gamma (PPARgamma) is a nuclear hormone receptor that has been shown to regulate differentiation and cell growth. Studies of the differentiative effects of PPARgamma agonists on several cancer cell lines led to the hypothesis that dysfunction of PPARgamma contributes to tumorigenesis. These functional observations were strengthened by genetic evidence: somatic loss-of-function mutations in PPARG, encoding PPARgamma, in sporadic colorectal carcinomas and somatic translocation of PAX8 and PPARG in follicular thyroid carcinoma. Recently overrepresentation of the H449H variant was found in a cohort of American patients with glioblastoma multiforme. The glioblastoma multiforme data suggest that PPARG contributes common, low-penetrance alleles for cancer susceptibility. To test this hypothesis in a broader range of cancers we examined a series of carcinomas of the cervix, endometrium, ovary, prostate, and kidney for germline sequence variation in PPARG. In addition to the two common sequence variants, P12A and H449H, there were five other sequence variants. P12A alleles were underrepresented in renal cell carcinoma patients compared to country-of-origin race-matched controls (3.75% vs. 12.1%, P<0.04). In contrast, the H449H variant was overrepresented in individuals with endometrial carcinoma compared to controls (14.4% vs. 6.25%, P<0.02). These observations lend genetic evidence consistent with our hypothesis that PPARG serves as a common, low-penetrance susceptibility gene for cancers of several types, especially those epidemiologically associated with obesity and fat intake.

Adenocarcinoma↗
PubMed2001

The role of 5-hydroxytryptamine1A and 5-hydroxytryptamine1B receptors in modulating spinal nociceptive transmission in normal and carrageenan-injected rats.

Single unit extracellular recordings from the dorsal horn neurons were obtained with glass micropipettes in pentobarbital-anesthetized rats. A total of 115 wide dynamic range (WDR) neurons were studied in 94 rats. In normal rats, the size of nociceptive receptive fields (RFs) of WDR neurons was approximately 123.3 +/- 8.21 mm2 (n = 88). Following carrageenan-induced inflammation, the RFs were markedly enlarged (332.4 +/- 30.1 mm2, n = 27, P < 0.001). The frequency of background activity of the WDR neurons in carrageenan-injected rats (11.3 +/- 2.1 imp/s, n = 27) was greater than that in normal rats (7.1 +/- 0.8 imp/s, n = 88, P < 0.05). In 82% of WDR neurons in normal rats, there was a separation between the A- and C-responses. In contrast, in 67% of the neurons in carrageenan-injected rats, the response to suprathreshold electrical stimuli was a long train with no separation between the A- and C-responses. In carrageenan-injected rats, the magnitude and duration of the nociceptive responses were significantly increased compared to those in normal rats, and the average C-response threshold (7.7 +/- 1.1 mA, n = 27) was lower than that in normal rats (10.4 +/- 0.7 mA, n = 88, P < 0.05). Intrathecal injection of the 5-hydroxytryptamine(1A) (5-HT1A) receptor agonist 8-hydroxy-DPAT hydroxybromide (8-OH-DPAT) (0.305, 1.525, 3.05, and 15.25 mM) dose-dependently increased Adelta- and C-responses and post-discharge in most of the WDR neurons. Following carrageenan-induced inflammation, the 8-OH-DPAT-induced facilitatory effect on Adelta- and C-responses and post-discharge was significantly enhanced (P < 0.05). Intrathecal injection of the 5-hydroxytryptamine1B (5-HT1) receptor agonist CGS12066A (0.222, 1.11, 2.22, and 11.1 mM) dose-dependently enhanced the C-response and post-discharge without influencing the Adelta-response. In carrageenan-injected rats, CGS12066A not only enhanced the facilitatory effect on the C-response and post-discharge, but also facilitated the Adelta-response. Intrathecal injection of the 5-HT(1A) receptor antagonist NAN-190 (0.2 mM) alone did not influence Adelta- and C-responses and post-discharge of WDR neurons in normal rats. When 0.2 mM NAN-190 was co-administered with 3.05 mM 8-OH-DPAT, the facilitatory effect of 8-OH-DPAT on Adelta- and C-responses and post-discharge was completely antagonized, whereas CGS12066A-induced facilitation on the C-response and post-discharge was not influenced by co-administration of 0.2 mM NAN-190 and CGS12066A. These data suggest that 5-HT1A and 5-HT1B receptor subtypes mediate the facilitatory effect of 5-HT on nociceptive processing in the spinal cord of rats. The excitability of dorsal horn WDR neurons and the sensitivity of the neurons to intrathecal 5-HT1A and 5-HT1B receptor agonists might increase following carrageenan-induced inflammation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2001

Tamoxifen abolishes estrogen's neuroprotective effect upon methamphetamine neurotoxicity of the nigrostriatal dopaminergic system.

The effects of 17beta-estradiol and the anti-estrogen, tamoxifen, on methamphetamine-induced neurotoxicity of the nigrostriatal dopaminergic system were examined in ovariectomized CD-1 mice. In Experiment 1, striatal dopamine concentrations from estrogen treated mice were significantly greater than that from non-estrogen treated mice following methamphetamine. Dopamine concentrations from estrogen+tamoxifen+methamphetamine treated mice were decreased compared to estrogen+methamphetamine treated mice and not significantly different from those of tamoxifen+methamphetamine treated mice or mice receiving methamphetamine alone. These results suggest that estrogen is functioning as a neuroprotectant of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity and that this neuroprotective effect of estrogen is abolished in the presence of tamoxifen. In Experiment 2, estrogen administration after methamphetamine treatment did not produce any significant changes in dopamine concentrations compared with methamphetamine treatment alone. The data from Experiment 2 show that estrogen cannot reverse the methamphetamine-induced neurotoxicity upon the nigrostriatal dopaminergic system. Similar results were observed for the potassium-stimulated dopamine outputs from these treatment conditions as evaluated with in vitro superfusion, although a difference between the two measures for the estrogen+methamphetamine treated group was obtained in Experiment 1. These results have important implications for estrogen-tamoxifen interactions upon the nigrostriatal dopaminergic system and the gender differences which are observed in Parkinson's disease and animal models of nigrostriatal dopaminergic neurotoxicity as well as for the proposed use of tamoxifen in pre-menopausal women at risk for breast cancer.

Animals↗