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T Reed

Publications and source records attributed to T Reed.

At least 37 records · Page 2Linked to original sources
PubMed1998

A novel E box/AT-rich element is required for muscle-specific expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene.

The cardiac/slow twitch sarcoplasmic reticulum (SR) Ca2+-ATPase gene (SERCA2 ) encodes a calcium transport pump whose expression is regulated in a tissue- and development-specific manner. Previously we have identified two distinct positive regulatory regions (bp -284 to -72 and -1815 to -1105) as important for SERCA2 promoter activity. Here we demonstrate that the SERCA2 distal promoter region functions like an enhancer by activating a heterologous promoter (TK) in a muscle cell-specific manner. Through deletion analysis a core enhancer region was delimited to the -1467 to -1105 bp fragment. We identified the E box/AT-rich element located at -1115 bp as critical for maximal enhancer activity. Gel mobility shift studies revealed that this E box/AT-rich element specifically binds a protein which is induced during Sol8 myogenesis. This region includes two other cis -acting elements, CArG and MCAT, which also bind specific nuclear protein complexes from Sol8 myotubes. Mutagenesis of each of these sites resulted in decreased SERCA/TK-CAT promoter activity. Based on these data, we propose that the E box/AT-rich element may contribute along with CArG and MCAT elements to the overall activation and regulation of the SERCA2 gene promoter.

3T3 Cells↗
PubMed1998

The moderating effect of self-esteem in reaction to voice: converging evidence from five studies.

It has been posited that high self-esteem persons (high SEs) are more confident than low self-esteem persons (low SEs) of their capability to provide meaningful input in a decision process. If this is so, then high SEs should be more influenced by their perceived level of voice, relative to low SEs. Survey data from 4 field studies showed that voice was more positively related to various dependent variables among high SEs than low SEs. In Study 5, the authors experimentally manipulated voice as well as participants' beliefs about their capability to provide meaningful input. As expected, voice had a greater impact on the reactions of participants who were led to believe that they were more capable of providing meaningful input. Theoretical implications are discussed.

Adolescent↗
PubMed1998

Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs), as detected by MRI, are common among the elderly and are frequently interpreted as representing a subclinical form of ischemic brain damage. We used volumetric MR techniques to investigate the contribution of genes and the environment to measures of brain morphology in a sample of community dwelling elderly male twins. METHODS: Brain MR (1.5 T) scans were obtained from 74 monozygotic (MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins born in the United States and age 68 to 79 when scanned. MR quantification used a previously published semiautomated segmentation algorithm to segment brain images into total brain, cerebrospinal fluid (CSF), and WMH volumes. Twin pair covariances were computed for each measure, and structural equation genetic models were fitted to these data. RESULTS: Total cranial, brain parenchyma, CSF, and WMH volumes were highly correlated in MZ pairs, and correlations in MZ pairs were significantly greater than those in DZ pairs. Structural equation modeling indicated heritabilities of 91%, 92%, and 73%, respectively, for total cranial, brain parenchyma, and WMH volumes. Correction for age and head size reduced the heritability of brain parenchyma to 62% (95% confidence interval, 56% to 68%) and the heritability of WMH volume to 71% (95% confidence interval, 66% to 76%). Proband concordance rates for large amounts of WMH were 61% in MZ pairs and 38% in DZ pairs, compared with a prevalence of 15% in the entire sample. CONCLUSIONS: This study is the first to quantify the relative contribution of genetic and individual environmental influences to measures of brain morphology in the elderly.

Aged↗
PubMed1998

Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male twins.

OBJECTIVE: To investigate the combined effect of the apolipoprotein E epsilon4 (ApoE*4) allele and midlife cardiovascular risk factors on cognitive decline. METHODS: Data are from the National Heart, Lung, and Blood Institute Twin Study-a longitudinal cardiovascular epidemiologic study of World War II male veteran twins currently in its 27th year of follow-up. Subjects were assessed for cardiovascular risk factors, including BP and glucose levels, at mean ages 48, 58, and 63 years. Participants in the current study are 410 individual twin subjects for whom cognitive function was measured twice, at ages 63 and 73 years. Ten-year change scores in performance on neuropsychological test examinations were adjusted for age, education, baseline score, and incident cardiovascular disease. RESULTS: For the sample as a whole, we observed a significant decline (p < 0.01) in cognitive performance over the 10 years of follow-up. ApoE*4 carriers with midlife hyperglycemia experienced the greatest decline in performance, which was also greater than expected from the separate effects combined. Midlife hypertension and ApoE*4, were each associated with excess decline in performance on tests of psychomotor speed. Their joint effect, however, was not greater than expected from the separate effects combined. CONCLUSIONS: ApoE*4 and midlife cardiovascular risk factors may have a synergistic effect on decline in cognitive function. This effect may be due to greater vascular or degenerative damage among subjects with ApoE*4.

Aged↗
PubMed1998

Association of midlife blood pressure to late-life cognitive decline and brain morphology.

OBJECTIVE: To investigate the association between midlife systolic blood pressure (SBP) and late-life cognitive decline and brain morphology in a sample of community-dwelling elderly men 68 to 79 years of age. METHODS: Subjects are surviving members from the prospective National Heart, Lung, and Blood Institute Twin Study (intake, 1969 to 1972) who, when examined for a fourth time in 1995 through 1997, underwent brain MRI and repeated assessment of neurobehavioral functioning. Quantification of the MR images determined cerebral volume and total volume of white matter hyperintensities (WMHIs) for 392 subjects. Midlife SBP levels measured in 1970, 1980, and 1985 were used to classify subjects into low, medium, and high midlife SBP categories. A 10-year change in performance on the Mini-Mental State Examination, Digit Symbol Substitution Test, Benton Visual Retention Test, and Verbal Fluency Test was also calculated for these subjects. For all reported analyses, patients were treated as genetically unrelated individuals. RESULTS: Subjects with high midlife SBP experienced a greater decline in cognitive performance and had larger WMHI volumes at follow-up in late life than did those with low midlife SBP. Decreased brain parenchyma and increased WMHI volumes were associated with decline in neurobehavioral functioning as measured in late life independent of age, education, and baseline levels of cognition. CONCLUSIONS: Midlife SBP is a significant predictor of both decline in cognitive function and MR volumetric measures of brain atrophy in late life. Because decline in neurobehavioral functioning was associated with decreased brain volume and increased WMHI volume, we conclude that the long-term impact of elevated SBP on decline in late-life neurobehavioral functioning is likely to be mediated through its chronic, negative effect on structural characteristics of the brain.

Adult↗
PubMed1997

Evidence that the apolipoprotein E-genotype effects on lipid levels can change with age in males: a longitudinal analysis.

We previously reported that change, with age, in plasma levels of total cholesterol (TC) and LDL cholesterol (LDL-C) differed between apolipoprotein E (APOE) genotypes epsilon 3 epsilon 3 and epsilon 3 epsilon 4, in a sample of 77 older, unrelated males. By use of a larger sample from that cohort, followed longitudinally during 1969-87, the change in TC and in LDL-C, between the epsilon 3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes, over three exams, was reanalyzed. Additionally, the change in triglycerides (TG) and in HDL-cholesterol (HDL-C), between the epsilon 3 epsilon 3 and epsilon 3 epsilon 4 APOE genotypes-as well as the differences between the epsilon 3 epsilon 3 and epsilon 3 epsilon 2 genotypes, for TC, LDL-C, TG, and HDL-C-were contrasted over the three exams. At exam 1 TG was higher in the epsilon 3 epsilon 4 group than in the epsilon 3 epsilon 3 group (mean age 48 years), and at exams 2 and exam 3 (mean ages 58 and 63 years, respectively) it was similar (P = .009 for the exam-by-genotype-interaction effect in the repeated-measures analysis). A similar trend was seen for TC (P = .03), yet previously detected LDL-C effects were not apparent (P = .46). Those with the epsilon 3 epsilon 2 genotype had higher TG and lower LDL-C and TC at each exam than were seen in those with the epsilon 3 epsilon 3 genotype, although the differences in the values were not always statistically significant. Differences in TC, LDL-C, and TG, between the epsilon 3 epsilon 2-genotype and epsilon 3 epsilon 3-genotype groups, did not significantly change over the three exams. HDL-C levels were relatively stable over the exams; however, the exam-by-genotype interaction was significant for the epsilon 3 epsilon 2 genotype versus the epsilon 3 epsilon 3 genotype (P = .02). The epsilon 4 allele effects on TG and TC changed between longitudinal exams and may be age dependent. Changes, with age, in the effect of the epsilon 3 epsilon 4 genotype on lipids may impact the risk of developing atherosclerotic disease.

Aged↗
PubMed1996

Multiple Sp1 binding sites in the cardiac/slow twitch muscle sarcoplasmic reticulum Ca2+-ATPase gene promoter are required for expression in Sol8 muscle cells.

The rabbit cardiac/slow twitch muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene encodes a Ca2+ transport pump whose expression is regulated during skeletal and cardiac muscle development and in response to various pathophysiological and hormonal states. Employing transient transfection analyses in Sol8 muscle cells, we have identified two positive regulatory regions, one distal (-1810 base pair (bp) to -1110 bp) and one proximal (-284 bp to -72 bp), within the SERCA2 promoter. The proximal promoter region from -284 bp to -80 bp was shown to confer muscle-specific expression to a heterologous promoter in Sol8 cells. This region is highly GC-rich containing the consensus sequence for four Sp1 elements (GGGCGG) and three Sp1-like elements (GGGAGG). DNase I footprint analysis with Sol8 nuclear extracts and purified Sp1 protein showed the protection of the seven Sp1 binding sites. In addition, site-directed mutagenesis of the Sp1 consensus sites demonstrated that Sp1 sites are essential for the muscle-specific expression of the SERCA2 promoter. Furthermore, we demonstrate that cotransfection of an Sp1 expression vector together with SERCA2-CAT constructs can up-regulate SERCA2 promoter activity. These results imply that the Sp1 transcription factor plays an important role in the transcriptional regulation of SERCA2 within muscle cells.

3T3 Cells↗
PubMed1996

Comparative diagnoses of twin zygosity by SSLP variant analysis, questionnaire, and dermatoglyphic analysis.

Zygosity diagnosis has been performed in 79 pairs of twins using three methods. Simple sequence repeat length polymorphism (SSLP) analysis allows an efficient classification (MZ or DZ) with only a few markers following a simplified technique of extraction and amplification. A method based on a full questionnaire completed by parents about twin similarity correctly classifies 97.46% of the pairs; 92.41% are correctly classified using only four questions as suggested by logistic regression analysis. The third method, using dermatoglyphic analyses, correctly classifies 86.76% of pairs. To lower the cost of DNA diagnosis we stress the possibility of limiting its use to pairs with scores in the overlap area between MZ and DZ twins with a validated questionnaire.

Child↗
PubMed1996

Genetic predisposition to organ-specific endpoints of alcoholism.

Medical records of the 15,924 twin-pairs in the National Academy of Sciences-National Research Council (NAS-NRC) twin registry were collected for an additional 16 years through 1994 when the surviving twins were aged 67 to 77 years. Compared with earlier analyses (Hrubec, Z, and Omenn, G. S., Alcohol. Clin. Exp. Res., 5:207-215, 1981), when subjects were aged 51 to 61, there were 23% more diagnoses of alcoholism (34.4 per 1,000 prevalence), 32% more diagnoses of alcoholic psychosis (5.4 per 1,000), and 25% more twins with liver cirrhosis (17.7 per 1,000). Overall, 5.3% of the cohort had at least one of the diagnoses related to alcoholism. Probandwise concordance rates (%) were: alcoholism-26.7 monozygotic (MZ), 12.2 dizygotic (DZ) (p < 0.0001); alcoholic psychosis-17.3 MZ, 4.8 DZ (p < 0.05); and cirrhosis-16.9 MZ, 5.3 DZ (p < 0.001). Concordance for any diagnosis related to alcoholism was 30.2 MZ, 13.9 DZ (p < 0.0001). Maximum-likelihood modeling indicated that approximately 50% of the overall variance was due to additive genetic effects; in all diagnosis categories, a totally environmental model gave a significantly poorer fit to the data. Bivariate and trivariate genetic analyses indicated most of the genetic liability for the organ-specific endpoints of psychosis and cirrhosis was due to the shared genetic liability for alcoholism. Once the shared variance with alcoholism was considered, there was no further shared genetic liability for psychosis and cirrhosis. Our results confirm Hrubec and Omenn's conclusion that there was significantly greater concordance in MZ twins-pairs for alcoholic psychosis and cirrhosis in the NAS-NRC twins, and concordance rates remained similar to those reported 16 years earlier. In contrast, we found most of the genetic liability to organ-specific complications of alcoholism was shared with the genetic liability for alcoholism per se; only a small portion of the genetic variance of the individual complications was independent of the genetic predisposition for alcoholism.

Aged↗
PubMed1995

Intrapair differences in personality and cognitive ability among young monozygotic twins distinguished by chorion type.

We evaluated placentation effects on behavioral resemblance of 44 pairs of monozygotic (MZ) twin children. Tested at ages 4-6, the twins' zygosity and placental type had been determined at their delivery. The sample included 23 monochorionic (MC) and 21 dichorionic (DC) MZ twin pairs: DC-MZ twins result from separation of blastomeres within 72 h of ovulation; MC-MZ twins arise from later duplication of the inner cell mass. Twins were individually administered the McCarthy Scales of Cognitive Ability, while their mothers separately rated each cotwin on an individualized 280-item form of the Personality Inventory for Children (PIC). Absolute differences between MC-MZ cotwins were smaller than those between DC-MZ cotwins for all 20 PIC scales, significantly so for 3 of 4 factor scales, 8 of 12 clinical scales, and 2 of 4 validity/screening scales from the PIC; in contrast, no consistent differences in intrapair resemblance of mono- and dichorionic MZ twins were found for the McCarthy Scales. The chorion differences found in the PIC data cannot be due to genetic differences, because all pairs are monozygotes; nor are they associated with differences in parity, gestational age, birth weight, maternal education, palmar dermatoglyphic asymmetry, or maternal knowledge of chorion type. We interpret our findings as suggestive evidence that variation in timing of embryological division, with effects on MZ twins' placental vasculature, has significant consequences for some dimensions of their behavioral development, as well.

Child↗
PubMed1995

On the association between adult blood pressure and dermatoglyphics as prenatal markers of development.

OBJECTIVE: To examine the relationships between finger and palm print (dermatoglyphic) features and, first, the presence or absence of hypertension, and, secondly, blood pressure levels in non-hypertensive subjects. METHODS: Prints were available from 841 male World War II veteran twins (393 pairs, 55 individual cotwins), who were born in the USA between 1917 and 1927 and examined three different times between 1969 and 1987. At each examination the hypertensive status was assessed by blood pressure measurement, use of antihypertensive medications and two physicians' diagnostic impressions. RESULTS: Subjects defined as hypertensive did not differ in dermatoglyphics from non-hypertensives for any trait examined. There were 60 twin-pairs discordant for hypertension; hypertensive cotwins showed lower ridge counts on the left hand, and this relationship was the opposite of what has previously been reported. Using only normotensive subjects at all three examinations, there was little consistent relationship between blood pressures (adjusted for age, body mass and alcohol consumption) and various dermatoglyphic features, except for lower palmar a-b ridge count in those with higher systolic blood pressure. CONCLUSIONS: Unless the in utero development of dermatoglyphics in relation to blood pressure is substantially different between singleton and twin pregnancies, there are no useful relationships between dermatoglyphics and hypertension or strong relationships between the presence of certain 'dermatoglyphic markers of impaired fetal development' and blood pressure in subjects who remain normotensive until early in their seventh decade.

Adult↗