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Biomedical subjects

T Reed

Publications and source records attributed to T Reed.

At least 19 recordsLinked to original sources

Long-term bone loss in men: effects of genetic and environmental factors.

OBJECTIVE: To identify environmental factors associated with bone loss in adult male twins and to determine the extent to which shared environmental characteristics affect estimates of the genetic influence on bone loss. DESIGN: A 16-year cohort study. SETTING: A midwestern university hospital. PARTICIPANTS: One hundred and eleven male veterans of World War II or the Korean conflict, born between 1916 and 1927. All were twins, with the sample comprising 48 pairs and 15 persons whose twin brothers were deceased or seriously ill. MEASUREMENTS: Bone mass and environmental characteristics (cigarette smoking, alcohol consumption, physical activity, dietary calcium intake, use of thiazide diuretics) measured at baseline and 16 years later. RESULTS: Rates of radial bone loss averaged 0.45% per year. Those who both smoked and used alcohol at levels greater than the median for the population had a rate of bone loss (10% in 16 years) twice the rate of those who were below the median level for both variables (5% bone loss, P = 0.003). Rates of bone loss were correlated within twin pairs, and these correlations were diminished 25% to 35% by adjustments for environmental influences on bone loss. However, statistically significant within-pair correlations remained (r = 0.4), which did not differ between monozygotic and dizygotic twin pairs after adjustments for smoking, alcohol use, dietary calcium intake, and exercise. CONCLUSIONS: Bone loss in men during mid-life is determined, at least in part, by environmental factors, including smoking, alcohol intake, and, possibly, physical activity. Rates of bone loss were similar within twin pairs, apparently because of a shared environment.

Alcohol Drinking

Neonatal 6-OHDA lesions and rearing in complex environments: regional effects on adult brain 14C-2-deoxyglucose uptake revealed by exposure to novel stimulation.

Behavioral and neuromorphological data have suggested at least a partial interaction between the effects of norepinephrine-depleting neonatal 6-OHDA lesions and the effects of rearing in enriched environments. The present study examined the impact of both of these early manipulations upon regional brain uptake of 14C-2-deoxyglucose (14C-2DG) in adulthood. Newborn rats received 6-OHDA (50 mg/kg s.c.) or vehicle and, after weaning at 25 days, were reared in isolated versus enriched conditions. Regional brain 14C-2DG uptake was then examined at 70-80 days of age--either in the home cage or while animals were being exposed to novel, presumably arousing, stimulation. Ninety-seven brain regions were examined in eight separate groups. Results indicated that (1) Under baseline conditions, neither neonatal 6-OHDA nor differential rearing conditions produced widespread alterations in regional brain 14C-2DG uptake profiles. An overall enrichment effect was seen on only five brain areas, with rats reared in enriched environments showing lower levels of 14C-2DG uptake (-20% to -30%) than isolated rats. Neonatal 6-OHDA produced no main effect on 14C-2DG uptake in any brain region. (2) In contrast, when 14C-2DG uptake was assessed during exposure to a novel environment, five brain areas showed differential 14C-2DG uptake in 6-OHDA-treated rats, and 20 brain areas showed differential uptake in rats reared in enriched conditions. (3) No significant interaction effect on brain regional 14C-2DG uptake was observed between neonatal 6-OHDA and environmental complexity factors. These results are consistent with the notion that enduring effects of rearing and early 6-OHDA treatment may, independently, relate to a general reactivity factor. They also indicate that some effects of early neurochemical injury and subsequent experiential factors may not be apparent under normal resting conditions, but only become evident in the presence of appropriate "activating" stimulation.

Animals

Effects of selective return on estimates of heritability for body mass index in the National Heart, Lung, and Blood Institute Twin Study.

In the National Heart, Lung, and Blood Institute Twin Study, body mass index (BMI) was studied at military induction and at three subsequent examinations spanning five decades in a cohort of white, male World War II veterans. At military induction (1940s) and again at the first clinical examination of this study (1969-1973), there was close agreement of three commonly used estimates of heritability (range 0.72 to 0.80), and no evidence of a difference in total variance of BMI between the zygosities. However, at the last two examinations (1980s), the total variance in dizygotic (DZ) twins was significantly greater than that of monozygotic (MZ) twins (P less than 0.01) and these same heritability estimates varied widely. The among-pair estimate of heritability fell to unrealistic negative values, the within-pair estimate rose to values of 1.0 or greater, and the intraclass correlation coefficient estimate was slightly lower than in the entire cohort at baseline. The cause of the unequal zygosity total variance appears to have been nonparticipation at later examinations of MZ twins with extreme values of BMI, with no evidence of a similar selection process influencing DZ twins. This selection process biased the three estimates of heritability, making it difficult to determine which estimate is the most appropriate. Despite these biases, it remains clear that genetic factors contribute substantially to BMI in this population.

Adult

Effects of placentation on selected Type A behaviors in adult males in the National Heart, Lung, and Blood Institute (NHLBI) twin study.

A dermatoglyphic index derived from monozygotic (MZ) twins of known placental type was used to estimate placentation retrospectively in a sample of adult male MZ twins. Examination of behavioral test scores with respect to placentation showed that the within-pair difference of most measures of type A behavior was smaller in presumed monochorionic than presumed dichorionic pairs. Measures of cognitive function and hostility were not related to placental type. Intraclass correlations in the monochorionic subgroup of MZ twins were greater than the correlations reported for the full sample of MZ twins. The trends were strongest for the Adjective Check List scales taken at two different exams 5 years apart and, to a lesser extent, for the Framingham type A scale. Our results are most consistent with greater intrauterine environmental covariance in monochorionic MZ twins as an explanation for inflation of the MZ twin correlation relative to dizygotic (DZ) correlation reported for some type A measures.

Adult

The NHLBI Twin Study: heritability of apolipoprotein A-I, B, and low density lipoprotein subclasses and concordance for lipoprotein(a).

Heritability of plasma apolipoprotein (apo) A-I, apo B, and low density lipoprotein (LDL) subclasses and concordance for lipoprotein(a) excess were assessed in 109 monozygotic (MZ) and 113 dizygotic (DZ) twin pairs participating in the third examination of the National Heart, Lung, and Blood Institute Twin Study. The intraclass correlation coefficient for apo A-I was significantly greater in MZ twins (0.56) than in DZ twins (0.37, P less than 0.05); however, apo A-I showed an unequal distribution in the two groups, with significantly greater total variance in DZ twins. Therefore the among-component estimate of genetic variance was applied, and the results indicated no significant heritability for apo A-I (P = 0.59). MZ and DZ twins had equal apo B variance. The intraclass correlation coefficient for apo B in MZ twins (0.71) was significantly higher than in DZ twins (0.25) (P less than 0.0001), indicating significant heritability for apo B. Plasma apo A-I levels were significantly correlated with alcohol intake (P less than 0.0001), body mass index (BMI, P less than 0.0001), and physical activity, while apo B levels were significantly correlated only with BMI (P less than 0.05). After plasma apo A-I and apo B concentrations were adjusted for all of these variables and for cigarette smoking, the analysis of variance and intraclass correlation coefficients remained virtually unchanged. The LDL type intraclass correlation coefficient was higher in MZ twins (0.58) than in DZ twins (0.32, P less than 0.005); however, greater total variance for this parameter in DZ twins was observed and after applying the among component estimate of genetic variance, no significant heritability of LDL type was observed. After adjustment for covariate effects the conclusions were not changed. Only 8.4% of MZ twin pairs, as compared with 26.7% of DZ twin pairs, were discordant for elevated lipoprotein(a) on gradient gels (P less than 0.0001). Our data indicate that there is a strong heritability for plasma apo B and lipoprotein(a), with only weak evidence for heritability of LDL type or plasma apo A-I levels within this population sample.

Aged

Concordance of ischemic heart disease in the NHLBI twin study after 14-18 years of follow-up.

Morbidity and mortality were assessed in the NHLBI twin study at the end of 1987. Deaths were greater in DZ twins (58/520, 11.2%) than MZ twins (38/508, 7.5%). Ischemic heart disease concordances were 2.3 times higher in MZ pairs and 2.8 times higher in DZ pairs than expected based on the prevalence of ischemic heart disease in the cohort. Family history scores for heart disease, calculated 14-18 years earlier at entry to the study, were significantly higher in DZ pairs where one or both members later developed ischemic heart disease and in corcordant MZ pairs than in twin-pairs without any subsequent heart disease. Concordance rates were not significantly different between MZ and DZ pairs. The results agree with previous suggestions that selection at enlistment into the armed services over 40 years ago, as well as later volunteering for the NHLBI twin study, resulted in a decline in the number of concordant MZ pairs.

Cause of Death

Influence of placentation on high density lipoproteins in adult males: the NHLBI twin study.

Dizygotic (DZ) World War II veteran twins who participated in the National Heart Lung and Blood Institute (NHLBI) Twin Study have been reported to have greater variance than monozygotic (MZ) twins for plasma high-density lipoprotein cholesterol (HDL-C), cholesterol in the low-density fraction of HDL (HDL2-C) and apolipoprotein A-I, a major protein component of HDL. It was hypothesized that a possible source of this difference in zygosity variance could be prenatal environmental influences related to placental type. Dermatoglyphics were used to provide a retrospective index of placental type in a subset of the NHLBI MZ twins aged 59-70. The MZ twins classified as dichorionic were found to have significantly greater within-pair variability than the monochorionic MZ twins for HDL-C, HDL2-C and Apo A-I. These findings indicate that intrauterine environmental influences on HDL are manifest later in life.

Aged

Genetic effects on cardiovascular responses to cold and mental activity in late adulthood.

The purpose of the present investigation was to examine the genetic contributions to cardiovascular reactivity in an adult cohort of male twins. A total of 47 monozygotic (MZ) twin pairs and 54 dizygotic (DZ) twin pairs, aged 59 to 69 years, were laboratory tested at four sites as part of the third examination of the National Heart, Lung, and Blood Institute Twin Study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded during two tasks, a mental arithmetic task involving serial subtraction and the cold pressor test. Significant cardiovascular responsivity was observed during both tasks as measured by substantial elevations in SBP, DBP, and HR from resting periods to task periods. Heritability estimates were statistically significant for SBP and DBP but not HR levels during pretask baseline periods and during both tasks. Genetic variance was maintained for blood pressure reactivity to the mental arithmetic task after adjustments for baseline and performance. No genetic variance for SBP or DBP reactivity to the cold pressor test was evident.

Aged

Attempted transcervical occlusion of the fallopian tube with the Nd:YAG laser.

A prospective multi-center trial was initiated to test the efficacy and safety of transcervical occlusion of the fallopian tube with the Nd:YAG laser. A multi-center approach was deemed necessary because of the large sample size required to test adequately the effectiveness of sterilization procedures. However, efforts to continue the study as designed were abandoned because, of the 17 subjects completing the study, only four (24%) had bilateral tubal occlusion at the site of laser treatment. We conclude that the hysteroscopic method, as tested, is inadequate to provide permanent sterilization. Modification of the technique or alterations in patient preparation may improve the outcome.

Adult

Hypothesis: association of the critical region of trisomy 18 and 18q2--syndrome with dermatoglyphic findings and a growth suppressor (deleted in colon cancer) locus.

Evidence from the literature is reviewed to suggest that when fingertip dermal ridge patterns in chromosomal deletion syndromes are characteristic of the opposite spectrum of the developmental scale from patterns found in cases trisomic for the same chromosomal region, the association may be a consequence of loci with growth regulatory functions. Evidence is presented that DNA markers at 18q21 should be the first candidate sequences to be used to test this hypothesis in families with fingertip arches segregating in an apparent autosomal dominant fashion.

Cell Transformation, Neoplastic

Estimates of heritability of plasma homocyst(e)ine levels in aging adult male twins.

Plasma homocyst(e)ine level was determined for 96 identical (MZ) and 92 fraternal (DZ) adult male twins aged 59-69. There was no difference in mean between MZ (10.31 nmol/ml) and DZ (10.36 nmol/ml) twins. The intraclass correlation coefficient of the log-transformed homocyst(e)ine level in 43 complete MZ and 39 complete DZ pairs was 0.55 and 0.19, respectively. The MZ correlation was significantly (p less than 0.05) greater than the DZ correlation, suggesting that the level of plasma homocyst(e)ine is genetically influenced.

Aged

Family history of ischemic heart disease with respect to mean twin-pair cholesterol and subsequent ischemic heart disease in the NHLBI twin study.

This study examines the independent and interactive effects of family history scores (FHxS) for the prevalence of ischemic heart disease with plasma lipids and subsequent morbidity and mortality from ischemic heart disease. FHxS were calculated for 514 sets of middle aged male twins who participated in the entry examination of the NHLBI Veteran twin study in 1969-1973. Comparison of the FHxS with the level of plasma total cholesterol and HDL cholesterol (HDLc) paralleled earlier reported findings in young adults; individuals with high total cholesterol in two exams 8-12 years apart had significantly (P less than .01) higher FHxS. The same relationship was noted when using the mean twin-pair cholesterol level at the initial exam when the twins were in their 40s. Using the pair means over two exams as the cotwins aged into their 50s, the association of FHxS with total cholesterol declined and pairs with HDLc persistently in the highest quintile at both exams had significantly (P less than .01) lower FHxS. The changes in the pattern of association of lipid fractions with FHxS with age parallel the reported age decline of total cholesterol as a risk factor for heart disease. Assessment of ischemic heart disease events up to January 1988 revealed a highly significant association (P less than .0001) of later ischemic heart disease events with FHxS. At each level of lipid categorization pairs who later had events had higher FHxS than those without any subsequent heart disease; these differences were significant in all but the low risk lipid groups (low total cholesterol, high HDLc, and low total cholesterol/HDLc ratio). We conclude that FHxS is related to total cholesterol and HDLc but also is an independent predictor of subsequent ischemic heart disease after 14-18 years of follow-up.

Adult

A comparative study of autistic subjects' performance at two levels of visual and cognitive perspective taking.

This study extended previous investigations of autistic subjects' perspective-taking abilities through a within-subjects contrast between two levels each of both visual and cognitive problems with stringent controls against guessing. When compared with normal and mentally retarded subjects', the autistic group's performance supported Baron-Cohen's (1988) hypothesis of a selective deficit for cognitive perspective taking among autistic subjects. Both levels of visual perspective taking demonstrated virtually unimpaired performance for autistic subjects with no significant difference between them and control groups. On the cognitive perspective-taking tasks, however, the performance of the three groups was significantly different, with the vast majority of autistic subjects unable to do even the most basic level of this task. Possible explanations and educational implications were discussed.

Adolescent

The transfer effect of leadup activities.

Previous literature shows that operative laboratory performance can be significantly improved through leadup training where students complete simulated preparations in plastic blocks. Since the task requirements of most fixed prosthodontic preparations seem similar to those of operative dentistry, it may be hypothesized that leadup training utilizing operative-like preparations would facilitate performance in the projects of both courses. The objective of this study was to test that hypothesis. The performance of students who had completed the leadup training nine months earlier was compared with that of randomly selected control groups, with replacement, in a subsequent operative and fixed prosthodontics course. Calibrated raters were unaware of group affiliation of products. Analyses of variance showed that students in the experimental group statistically significantly outperformed those in the control group on the two operative preparations which were most like products completed during the leadup training. There was no such difference for any of the three fixed prosthodontics products. It is concluded that transfer of training is highly specific and that leadup training must simulate the criterion in both its cognitive and motor components, if it is to have a facilitating effect.

Analysis of Variance

Quantitative twin analysis of radial and ulnar ridge counts and ridge count diversity.

Analysis of variance was performed on the radial and ulnar finger ridge counts and ridge count diversity index in 360 twin sets from which estimates of genetic variance were obtained. Findings for radial and ulnar counts paralleled those previously obtained for finger pattern type and ridge count (larger of radial and ulnar count). In contrast, ridge count diversity showed no indication of unequal total variances, as previously found for the total ridge count. One must be cautious not to exclude genetic influences on traits, such as the thumb variables in this study, where there are unequal total variances between monozygotic and dizygotic twins and the more conservative estimate of genetic variance is not significant.

Analysis of Variance

Genetic linkage analysis of hemoglobin variants in 175 families.

Linkage analysis using the LIPED program developed by Ott for the analysis of whole family data was performed on 175 families with variants of the hemoglobin beta- or gamma-chain. Comparison of our results with those in the literature indicate that there is little evidence for linkage with any of the currently used markers, although there is considerable heterogeneity in lod scores between sexes for the Duffy and MNS blood groups. It is suggested that the most successful approach in the future will be to analyze markers known to be localized on chromosomes which have been indicated as likely sites of the beta-chain locus from hybridization studies.

Duffy Blood-Group System