Biomedical subjects

Jennie Z Ma

Publications and source records attributed to Jennie Z Ma.

At least 19 recordsLinked to original sources

PubMed2006

A genomewide search finds major susceptibility loci for nicotine dependence on chromosome 10 in African Americans.

Epidemiological studies have demonstrated that genetic factors account for at least 50% of the liability for nicotine dependence (ND). Although several linkage studies have been conducted, all samples to date were primarily of European origin. In this study, we conducted a genomewide scan of 1,261 individuals, representing 402 nuclear families, of African American (AA) origin. We examined 385 autosomal microsatellite markers for ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerstrom Test for ND (FTND). After performing linkage analyses using various methods implemented in the GENEHUNTER and S.A.G.E. programs, we found a region near marker D10S1432 on chromosome 10q22 that showed a significant linkage to indexed SQ, with a maximum LOD score of 4.17 at 92 cM and suggestive linkage to HSI, SQ, and log-transformed SQ. Additionally, we identified three regions that met the criteria for suggestive linkage to at least one ND measure: on chromosomes 9q31 at marker D9S1825, 11p11 between markers D11S1993 and D11S1344, and 13q13 between markers D13S325 and D13S788. Other locations on chromosomes 15p11, 17q25, and 18q12 exhibited some evidence of linkage for ND (LOD >1.44). The four regions with significant or suggestive linkage were positive for multiple ND measures by multiple statistical methods. Some of these regions have been linked to smoking behavior at nominally significant levels in other studies, which provides independent replication of the regions for ND in different cohorts. In summary, we found significant linkage on chromosome 10q22 and suggestive linkage on chromosomes 9, 11, and 13 for major genetic determinants of ND in an AA sample. Further analysis of these positive regions by fine mapping and/or association analysis is thus warranted. To our knowledge, this study represents the first genomewide linkage scan of ND in an AA sample.

Adolescent↗

PubMed2006

Gene-based analysis suggests association of the nicotinic acetylcholine receptor beta1 subunit (CHRNB1) and M1 muscarinic acetylcholine receptor (CHRM1) with vulnerability for nicotine dependence.

Based on our previously identified linkage regions for nicotine dependence (ND), we selected six and five single nucleotide polymorphisms (SNPs) in the muscarinic cholinergic receptor subtype M1 (CHRM1) and nicotinic cholinergic receptor beta1 (CHRNB1), respectively, to determine the association of the two genes with ND in a total of 2,037 subjects from 602 nuclear families of either African-American (AA) or European-American (EA) origin. Individual SNP- and/or haplotype-based analyses indicated that the CHRNB1 was significantly associated with ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström Test for ND (FTND), in both ethnic samples. The association of rs2302763 in the CHRNB1 was significant with adjusted SQ in the EA sample after correction for multiple testing (P=0.013). Haplotype A-T-A formed by SNPs rs2302765, rs2302762, and rs9217 in the CHRNB1 was significantly associated with the high risk allele for all the three ND measures (minimum P=0.009, 0.006, and 0.008 for SQ, HSI and FTND, respectively) in the AA sample while haplotype A-T-A formed by rs2302765, rs2302763, and rs9217 was significantly positively associated with ND (minimum P=0.005, 0.016, and 0.016 for SQ, HSI and FTND, respectively) in the EA sample. The CHRM1 exhibited significant protective associations of haplotype C-C-A-T-G-G formed by all six SNPs of this gene with at least one ND measure in the AA sample after Bonferroni correction (minimum P=0.008, 0.013, and 0.009 for SQ, HSI and FTND, respectively), but no significant association was found in the EA sample. The significant associations, together with their location of linked region to ND, suggest that the CHRNB1 and CHRM1 are likely candidates for further investigation.

Adult↗

PubMed2006

Association of specific haplotypes of neurotrophic tyrosine kinase receptor 2 gene (NTRK2) with vulnerability to nicotine dependence in African-Americans and European-Americans.

BACKGROUND: The gene encoding neurotrophic tyrosine kinase receptor 2 (NTRK2) has been localized to a region on chromosome 9q22-q23 that showed a "suggestive" linkage to nicotine dependence (ND) in our previous linkage analyses. However, no association of NTRK2 with ND has been identified. METHODS: Family-based association analyses of 2037 participants (1366 African Americans [AA], 671 European Americans [EA]) representing 602 nuclear families were performed to evaluate association of nine single nucleotide polymorphisms (SNPs) within NTRK2 with ND. RESULTS: Individual SNP-based association analysis indicated that in the EA sample, SNPs rs1659400 and rs1187272 were significantly associated with at least one adjusted ND measure. Haplotype analysis revealed that even after Bonferroni correction, the haplotype T-T-A of rs1659400-rs1187272-rs1122530 had a highly significant positive association, with adjusted ND measures in the EA sample (max Z = 3.78; p = .0001, frequency 59.9%). We further identified a major haplotype, T-G-C-A-A (26%), formed by rs993315-rs736744-rs920776-rs4075274-rs729560, which showed a significant positive association (max Z = 2.97, p = .003) with adjusted ND measures in the AA sample. CONCLUSIONS: These results strongly suggest that NTRK2 is a susceptibility gene for ND. These findings imply that NTRK2 plays a role in the etiology of ND and represents an important biological candidate for further investigation.

Adult↗

PubMed2006

Prevalence of osteopenia and osteoporosis by central and peripheral bone mineral density in men with prostate cancer during androgen-deprivation therapy.

OBJECTIVES: To determine the prevalence of osteopenia and osteoporosis by central (spine and hip) and peripheral (radius) bone mineral density (BMD) in men with prostate cancer undergoing androgen-deprivation therapy (ADT). Low BMD and fractures are prevalent in this group of men. Most published studies on ADT-related bone loss have documented the loss of BMD in the spine and hip as measured by dual x-ray absorptiometry. In one study, the loss of BMD was most pronounced at the radius. METHODS: In a chart review of patients receiving ADT, the spine and hip BMD results were recorded in 89 patients. Of these 89 patients, the BMD of the radius was also recorded in 53. RESULTS: In the 89 patients with BMD measurements of the spine and hip, 24 (26.9%) had osteoporosis of the hip or spine as defined by a T score of -2.5 or less, and 45 patients (50.6%) had osteopenia (T score -1.0 to -2.5). In the subset of 53 patients who also had the BMD of the radius measured, the results of the BMD of the radius changed the category of diagnosis in 18 patients (34%). The prevalence of osteoporosis increased from 25% to 53% when the results of the radius were included. CONCLUSIONS: Men with prostate cancer treated with ADT have a high prevalence of osteopenia and osteoporosis as determined by peripheral and central BMD measurements. The use of the peripheral BMD measurement appears to identify more patients with osteoporosis and suggests its use in the evaluation of osteoporosis in men receiving ADT.

Aged↗

PubMed2006

Significant association of catechol-O-methyltransferase (COMT) haplotypes with nicotine dependence in male and female smokers of two ethnic populations.

The catechol-O-methyltransferase (COMT) gene plays a prominent role in dopaminergic circuits central to drug reward. Allelic variants within the COMT gene are therefore potential candidates for examining interindividual differences in vulnerability to nicotine dependence (ND). We analyzed five single nucleotide polymorphisms (SNPs), including the Val/Met variant (rs4680), which results in a three- to four-fold difference in enzyme activity within COMT, for association with the three ND measures, SQ, HSI, and FTND, in 602 nuclear families of African-American (AA) or European-American (EA) origin. The Val/Met variant showed a significant association with the three ND measures in the pooled and EA samples and with FTND in the AA sample. Haplotype analysis revealed a major protective A-G-T haplotype (frequency 23.6%) for rs740603-rs4680-rs174699 in the AA sample (minimum Z=-3.35; P=0.0005 for FTND), a major protective T-G-T haplotype (frequency 15.2%; minimum Z=-2.92; P=0.003 for FTND) in the EA sample, and a high-risk C-A-T haplotype (frequency 16.9%; minimum Z=3.16; P=0.002 for SQ) in the AA sample for rs933271-rs4680-rs174699. Furthermore, we found that the significant haplotypes within COMT were gender-specific and the significantly associated A-G-T is protective in AA females only, whereas T-G-T is protective in EA males only. Moreover, we found a major high-risk T-A-T haplotype (frequency 56.7%) that showed significant association with the three ND measures in EA males. Further examination of two protective haplotypes, A-G-T in AAs and T-G-T in EAs, indicated that the low COMT enzyme activity Met allele is protective to become nicotine dependent. In summary, our results provide evidence for a role of COMT in the susceptibility to ND and further confirm that its effect is ethnic and gender specific.

Adult↗

PubMed2006

Obesity and survival in a cohort of predominantly Hispanic children with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL), the most common malignancy in children, constitutes 25% of all pediatric cancer. Childhood cancer patients who are obese at diagnosis represent a particular challenge for the oncologist. Obesity may complicate chemotherapy dose determination, and has been associated with decreased overall and event-free survival in a number of adult cancer patients, and more recently in pediatric patients. The purpose of the present study was to examine whether obesity at diagnosis was associated with decreased overall and event-free survival in a cohort of 322 predominantly Hispanic pediatric patients with B-precursor ALL. Obesity was classified as an age-standardized and sex-standardized body mass index z-score at or above the 95th percentile. Hazard ratios (HRs) for overall and event-free survival were assessed using Cox proportional hazards regression modeling. Obesity at diagnosis was not associated with decreased overall survival (HR = 1.40, 95% confidence interval = 0.69-2.87) or event-free survival (HR = 1.08, 95% confidence interval = 0.65-1.82) in the overall cohort or in either of the 2 age-at-diagnosis (2 to 9 y; 10 to 18 y) subgroups. Our finding of no obesity-related prognostic effect in the overall cohort and in the under 2 to 9-year age-at-diagnosis cohort was consistent with the previous large-scale study of ALL patients; the absence of a prognostic effect in the 10 to 18-year age-at-diagnosis cohort, however, conflicted with previous findings.

Adolescent↗

PubMed2005

Significant association of BDNF haplotypes in European-American male smokers but not in European-American female or African-American smokers.

Brain-derived neurotrophic factor (BDNF) influences dopamine and serotonin neurotransmission in the brain, both of which are involved in the reward system of addiction. The BDNF gene is located in a genomic region on chromosome 11p where we and others have found 'significant' linkage to nicotine dependence (ND). We tested the potential role of variants within BDNF in vulnerability to ND, which was assessed by Smoking Quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström Test for ND (FTND). Six single nucleotide polymorphisms (SNPs) in BDNF were analyzed in an extensively phenotyped cohort of 602 nuclear families with smokers and non-smokers of African-American (AA) or European-American (EA) ancestry. Individual SNP analysis revealed that two SNPs in the pooled male and three SNPs in the EA male samples were significantly associated with at least one adjusted ND measure. However, none of these associations remained significant after correction for multiple testing. Haplotype analysis of rs6484320-rs988748-rs2030324-rs7934165 revealed that a major T-C-T-G haplotype was significantly associated, even after Bonferroni correction, with the three ND measures in the pooled and EA male samples (maximum Z = 3.00, P = 0.002 and maximum Z = 3.13, P = 0.0009 for SQ, respectively). No significant association of a major haplotype with ND was found in the AA or EA female smokers. The significant association of BDNF variants with ND implies that this gene plays a role in the etiology of ND in EAs and that its involvement is gender specific. BDNF may warrant further investigation in ND.

Adult↗

PubMed2005

Improvement of mapping accuracy by unifying linkage and association analysis.

It is well known that pedigree/family data record information on the coexistence in founder haplotypes of alleles at nearby loci and the cotransmission from parent to offspring that reveal different, but complementary, profiles of the genetic architecture. Either conventional linkage analysis that assumes linkage equilibrium or family-based association tests (FBATs) capture only partial information, leading to inefficiency. For example, FBATs will fail to detect even very tight linkage in the case where no allelic association exists, while a violation of the assumption of linkage equilibrium will result in biased estimation and reduced efficiency in linkage mapping. In this article, by using a data augmentation technique and the EM algorithm, we propose a likelihood-based approach that embeds both linkage and association analyses into a unified framework for general pedigree data. Relative to either linkage or association analysis, the proposed approach is expected to have greater estimation accuracy and power. Monte Carlo simulations support our theoretical expectations and demonstrate that our new methodology: (1) is more powerful than either FBATs or classic linkage analysis; (2) can unbiasedly estimate genetic parameters regardless of whether association exists, thus remedying the bias and less precision of traditional linkage analysis in the presence of association; and (3) is capable of identifying tight linkage alone. The new approach also holds the theoretical advantage that it can extract statistical information to the maximum extent and thereby improve mapping accuracy and power because it integrates multilocus population-based association study and pedigree-based linkage analysis into a coherent framework. Furthermore, our method is numerically stable and computationally efficient, as compared to existing parametric methods that use the simplex algorithm or Newton-type methods to maximize high-order multidimensional likelihood functions, and also offers the computation of Fisher's information matrix. Finally, we apply our methodology to a genetic study on bone mineral density (BMD) for the vitamin D receptor (VDR) gene and find that VDR is significantly linked to BMD at the one-third region of the wrist.

Algorithms↗

PubMed2005

Reductions in and relations between "craving" and drinking in a prospective, open-label trial of ondansetron in adolescents with alcohol dependence.

Recently, we reported that ondansetron (a 5-HT3 antagonist) as an adjunct to cognitive behavioral therapy (CBT) produced significant within-group decreases (improvement) in drinking in adolescents with alcohol dependence. We previously have hypothesized that the mechanism of ondansetron treatment response in adolescents with alcohol dependence should be similar to early onset adult alcoholics, wherein blockade of serotonin-3 receptors may decrease dopamine release and subsequent alcohol consumption and craving. We now suggest that one mechanism by which ondansetron diminishes drinking in adolescents with alcohol dependence is through a reduction in "craving" as measured by the Adolescent Obsessive-Compulsive Drinking Scale (A-OCDS). We conducted an 8-week, prospective, open-label study of ondansetron (4 microg/kg b.i.d.) in 12 adolescents (age 14-20 years) who had alcohol dependence. Results showed that "irresistibility" and total scores as measured by the A-OCDS were correlated significantly with drinking indices (drinks/day, percent days abstinent) at the end of treatment, and that "irresistibility" and total A-OCDS scores decreased significantly by the end of treatment. These preliminary results suggest that the A-OCDS can be useful as an outcome measure in clinical studies of adolescents with alcohol dependence.

Adolescent↗

PubMed2005

Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence.

DOPA decarboxylase (DDC; also known as L-amino acid decarboxylase; AADC) is involved in the synthesis of dopamine, norepinephrine and serotonin. Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, the DDC gene is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND). Further, this gene is located within the 7p11 region that showed a 'suggestive linkage' to ND in our previous genome-wide scan in the Framingham Heart Study population. In the present study, we tested eight single nucleotide polymorphisms (SNPs) within DDC for association with ND, which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerstrom test for ND (FTND) score, in a total of 2037 smokers and non-smokers from 602 nuclear families of African- or European-American (AA or EA, respectively) ancestry. Association analysis for individual SNPs using the PBAT-GEE program indicated that SNP rs921451 was significantly associated with two of the three adjusted ND measures in the EA sample (P=0.01-0.04). Haplotype-based association analysis revealed a protective T-G-T-G haplotype for rs921451-rs3735273-rs1451371-rs2060762 in the AA sample, which was significantly associated with all three adjusted ND measures after correction for multiple testing (min Z=-2.78, P=0.006 for HSI). In contrast, we found a high-risk T-G-T-G haplotype for a different SNP combination in the EA sample, rs921451-rs3735273-rs1451371-rs3757472, which showed a significant association after Bonferroni correction with the SQ and FTND score (max Z=2.73, P=0.005 for FTND). In summary, our findings provide the first evidence for the involvement of DDC in the susceptibility to ND and, further, reveal the racial specificity of its impact.

Adult↗

PubMed2005

Ethnic- and gender-specific association of the nicotinic acetylcholine receptor alpha4 subunit gene (CHRNA4) with nicotine dependence.

We tested six single nucleotide polymorphisms (SNPs) in the alpha4 subunit gene (CHRNA4) and four SNPs in the beta2 subunit gene (CHRNB2) of nicotinic acetylcholine receptors (nAChRs) for association with nicotine dependence (ND), which was assessed by smoking quantity (SQ), the heaviness of smoking index (HSI) and the Fagerstrom test for ND (FTND) in 2037 subjects from 602 nuclear families of either European-American (EA) or African-American (AA) ancestry. Analysis of the six SNPs within CHRNA4 demonstrated that in the EA sample SNPs rs2273504 and rs1044396 are significantly associated with the adjusted SQ and FTND score, respectively. In the AA samples, SNPs rs3787137 and rs2236196 are each significantly associated with at least two adjusted ND measures. Association of rs2236196 with the adjusted HSI and FTND scores in the AA samples remained significant after correction for multiple testing. Furthermore, analysis revealed gender- and ethnic-specific associations for several SNPs with ND measures in both ethnic samples; however, only the association of SNP rs2236196 with the three adjusted ND measures remained significant after correcting for multiple testing in the AA female samples. Haplotype analysis of rs2273505-rs2273504-rs2236196 showed significant association after Bonferroni correction of a C-G-G haplotype (53.4%) with three adjusted ND measures in samples from the AA females. A similar analysis for the four SNPs within CHRNB2 did not reveal significant association with the three ND measures. In summary, our findings provide convincing evidence for the involvement of the nAChR alpha4 subunit, but not of the nAChR beta2 subunit, in nicotine addiction.

Black People↗

PubMed2005

Single- and multilocus allelic variants within the GABA(B) receptor subunit 2 (GABAB2) gene are significantly associated with nicotine dependence.

Twelve single-nucleotide polymorphisms (SNPs) in the human gamma-aminobutyric acid type B (GABA(B)) receptor subunit 2 gene (GABAB2) were tested for association with nicotine dependence (ND) in an extensively phenotyped cohort of 1,276 smokers and nonsmokers, representing approximately 404 nuclear families of African American (AA) or European American (EA) origin. The GABAB2 gene encodes a subunit of the GABA(B) receptor for GABA, an inhibitory neurotransmitter involved in the regulation of many physiological and psychological processes in the brain. The gene is located within a region of chromosome 9q22 that showed a "suggestive" linkage to ND. Individual SNP analysis performed using the PBAT-GEE program indicated that two SNPs in the AAs and four SNPs in the EAs were significantly associated with ND. Haplotype analysis using the Family-Based Association Test revealed that, even after Bonferroni correction, the haplotype C-C-G of rs2491397-rs2184026-rs3750344 had a significant positive association with ND in both the pooled and the AA samples. In the EAs, we identified two haplotypes, C-A-C-A and T-A-T-A, formed by SNPs rs1435252-rs378042-rs2779562-rs3750344, that showed a highly significant negative and positive association with ND, respectively. In summary, our findings provide evidence of a significant association of GABAB2 variants with ND, implying that this gene plays an important role in the etiology of this drug addiction.

Adult↗

PubMed2005

Fine mapping functional sites or regions from case-control data using haplotypes of multiple linked SNPs.

Previously, we reported an algorithm for scanning a large number of tightly linked single nucleotide polymorphisms (SNPs) for LD mapping of functional sites or regions from a family-based association design. In the present study, we extend our method to a case-control design. We first use the expectation maximization (EM) algorithm to estimate haplotype frequencies of multiple linked SNPs, and follow this by constructing a contingency table statistic S for LD analysis, based on the estimated haplotype frequencies. An empirical p-value is obtained based on the null distribution of the maximum of S (S*) from a large number (e.g., 1,000 or more) of randomized permutations. The proposed algorithm has been implemented in a computer program in which window searching for functional SNP sites can cover any number of loci without limitation, except that of computer storage. Unlike other programs for a case-control design that always conduct tests at a fix window width, in our program after setting a maximum size of haplotype window width, for a given maximum window width all possible widths of haplotypes are utilized to find the maximum statistic S * for each locus under investigation. The sensitivity of the proposed algorithm has been examined with simulated and real genotyping datasets. Association analyses indicate that our program is powerful enough to detect most, if not all, functional SNPs simulated in the original model or identified in the original report. Moreover, the program is very flexible and can be used in either regional or genome-wide scanning for association analysis with SNP markers.

Algorithms↗

PubMed2004

Time-dependent changes in transcriptional profiles within five rat brain regions in response to nicotine treatment.

Many years of behavioral and neurobiology studies have demonstrated broad physiological and pharmacological effects of nicotine on the central nervous system (CNS). However, the gene expression profiles associated with these effects are largely unknown. In this study, we characterized gene expression profiles in the prefrontal cortex, striatum, hypothalamus, amygdala and ventral tegmental area of the rat brain in response to subacute and chronic systemic nicotine administration using a pathway-focused microarray developed in this laboratory that contains 638 sequence-verified genes representing broad, yet targeted, biological functions. By comparing the regional effects of nicotine treatment on gene expression levels, we derived the expression profiles of targeted genes and gene families responding to the new environment created by nicotine throughout the complex connections of the CNS. While the expression of many genes was modulated by nicotine in several regions, only a few were co-modulated in multiple brain regions, suggesting region-specific transcriptional responses. Cluster analysis of significantly altered genes within each brain region over the course of nicotine treatment indicated the genes could be grouped into clusters. Subsequent ANOVA analysis demonstrated these clusters within each brain region to be significantly different at most time points. The clusters were comprised of broad functional groups, such as signaling, neurotransmission and protein modifications, demonstrating unique expression patterns within each region. Using a systematic approach to compare the different regional responses to nicotine administration will eventually provide a better understanding of how the different brain regions responding to this drug.

Amygdala↗

PubMed2004

Nicotine coregulates multiple pathways involved in protein modification/degradation in rat brain.

Previously, we used cDNA microarrays to demonstrate that the phosphatidylinositol and MAP kinase signaling pathways are regulated by nicotine in different rat brain regions. In the present report, we show that, after exposure to nicotine for 14 days, ubiquitin, ubiquitin-conjugating enzymes, 20S and 19S proteasomal subunits, and chaperonin-containing TCP-1 protein (CCT) complex members are upregulated in rat prefrontal cortex (PFC) while being downregulated in the medial basal hypothalamus (MBH). In particular, relative to saline controls, ubiquitins B and C were upregulated by 33% and 47% (P<0.01), respectively, in the PFC. The proteasome beta subunit 1 (PSMB1) and 26S ATPase 3 (PSMC3) genes were upregulated in the PFC by 95% and 119% (P<0.001), respectively. In addition to the protein degradation pathway of the ubiquitin-proteasome complexes, we observed in the PFC an increase in the expression of small, ubiquitin-related modifiers (SUMO) 1 and 2 by 80% and 33%, respectively (P<0.001), and in 3 of 6 CCT subunits by up to 150% (P<0.0001). To a lesser extent, a change in the opposite direction was obtained in the expression of the same gene families in the MBH. Quantitative real-time RT-PCR was used to validate the microarray results obtained with some representative genes involved in these pathways. Taken together, our results suggest that, in response to systemic nicotine administration, the ubiquitin-proteasome, SUMO, and chaperonin complexes provide an intricate control mechanism to maintain cellular homeostasis, possibly by regulating the composition and signaling of target neurons in a region-specific manner.

Animals↗

PubMed2004

A prospective, open-label trial of ondansetron in adolescents with alcohol dependence.

Ondansetron has been shown to be effective in the treatment of early-onset adult alcohol dependence. To date, no studies have been conducted in adolescents with alcohol dependence to assess the feasibility, safety, tolerability, and potential utility of ondansetron treatment. We conducted an 8-week, prospective, open-label study of ondansetron (4 microg/kg b.i.d.) in 12 adolescents who had alcohol dependence. Oral ondansetron was safe and well tolerated in our sample. Adverse events were mild and resolved quickly without intervention. No subjects discontinued due to adverse events. Intent-to-treat analyses showed a significant within-group decrease (improvement) for drinks/drinking day (t=-3.10, df=11, p=0.01), as well as decreases in drinks/day (t=-2.01, df=11, p=0.06) and percentage of days abstinent (t=1.45, df=11, p=0.18). These preliminary data suggest that ondansetron is safe and well tolerated in adolescents with alcohol dependence. Findings of decreased drinking underscore the need for future double-blind, placebo-controlled studies in this adolescent population.

Adolescent↗

PubMed2004

Long-term outcome of renal transplant recipients in the United States after coronary revascularization procedures.

BACKGROUND: Retrospective studies in dialysis patients have reported increased survival after coronary artery bypass (CAB) compared with coronary artery stenting and PTCA. The purpose of this study was to compare the long-term outcome of renal transplant recipients after stent, PTCA, or CAB with or without internal mammary grafting (CAB [IMG+] or CAB [IMG-]). METHODS AND RESULTS: Renal transplant recipients hospitalized from 1995 to 1999 for first coronary revascularization procedure were retrospectively identified from the United States Renal Data System database. Event-free survival for the end points of all-cause death, cardiac death, acute myocardial infarction (AMI), and the combined end point of cardiac death or AMI was estimated by the life-table method. The impact of independent predictors on survival was examined in a comorbidity-adjusted Cox model. In-hospital mortality rate was 2.3% for 909 stent patients, 4.3% for 652 PTCA patients, 9.4% for 288 CAB (IMG-) patients, and 5.0% for 812 CAB (IMG+) patients. Two-year all-cause survival (+/-SE) was: stent, 82.5+/-2.8%; PTCA, 81.6+/-3.1%; CAB (IMG-), 74.4+/-5.4%; and CAB (IMG+), 82.7+/-2.8%. The relative risks of all-cause and cardiac death were not significantly different among revascularization groups. The relative risk of cardiac death or AMI (versus PTCA) was 0.90 (95% CI, 0.69 to 1.17) for stent, 0.80 (95% CI, 0.55 to 1.17) for CAB (IMG-), and 0.57 (95% CI, 0.42 to 0.76) for CAB (IMG+). CONCLUSIONS: Renal transplant recipients in the United States have comparable long-term survival after percutaneous and surgical coronary revascularization procedures. The most favorable long-term outcome occurs after surgical coronary revascularization.

Adult↗

PubMed2004

Application of a customized pathway-focused microarray for gene expression profiling of cellular homeostasis upon exposure to nicotine in PC12 cells.

Maintenance of cellular homeostasis is integral to appropriate regulation of cellular signaling and cell growth and division. In this study, we report the development and quality assessment of a pathway-focused microarray comprising genes involved in cellular homeostasis. Since nicotine is known to have highly modulatory effects on the intracellular calcium homeostasis, we therefore tested the applicability of the homeostatic pathway-focused microarray on the gene expression in PC-12 cells treated with 1 mM nicotine for 48 h relative to the untreated control cells. We first provided a detailed description of the focused array with respect to its gene and pathway content and then assessed the array quality using a robust regression procedure that allows for the exclusion of unreliable measurements while decreasing the number of false positives. As a result, the mean correlation coefficient between duplicate measurements of the arrays used in this study (control vs. nicotine treatment, three samples each) has increased from 0.974+/-0.017 to 0.995+/-0.002. Furthermore, we found that nicotine affected various structural and signaling components of the AKT/PKB signaling pathway and protein synthesis and degradation processes in PC-12 cells. Since modulation of intracellular calcium concentrations ([Ca(2+)](i)) and phosphatidylinositol signaling are important in various biological processes such as neurotransmitter release and tissue pathogenesis including tumor formation, we expect that the homeostatic pathway-focused microarray potentially can be used for the identification of unique gene expression profiles in comparative studies of drugs of abuse and diverse environmental stimuli, such as starvation and oxidative stress.

Animals↗