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Biomedical subjects

T E Reed

Publications and source records attributed to T E Reed.

At least 19 recordsLinked to original sources

Detection of benzo(a)pyrene diol epoxide-DNA adducts in sperm of men exposed to cigarette smoke.

OBJECTIVE: To determine whether the adducts formed when benzo(a)pyrene, a diol epoxide derivative, binds covalently to DNA (BPDE-DNA adducts) are detectable in the sperm of men who smoke cigarettes. DESIGN: Prospective study. SETTING: The Toronto Hospital IVF-ET program. PATIENT(S): Twenty-three patients with normal seminal parameters: 11 smokers (20.6 +/- 0.7 cigarettes per day) and 12 nonsmokers. INTERVENTION(S): Semen samples obtained by masturbation. MAIN OUTCOME MEASURE(S): Seminal plasma samples were assessed for cotinine by RIA. Sperm were treated with dithiothreitol to release disulfide bonds and allow for DNA binding, then exposed to an anti-BPDE monoclonal antibody, a biotinylated antibody, and streptavidin-conjugated peroxidase. Staining intensity scores, determined in 100 cells per individual, were correlated with seminal plasma cotinine levels, a marker of smoking. RESULT(S): Cotinine levels correlated highly with the number of cigarettes smoked per day. Mean cotinine levels and mean staining intensity scores were higher in smokers than in nonsmokers. Staining intensity correlated highly with cotinine levels. CONCLUSION(S): We demonstrated, for the first time, that BPDE-DNA adducts in sperm cells are increased by smoking; we also detected comparatively high levels in nonsmokers, which indicates that environmental exposure also is substantial. The formation of adducts in spermatozoa is a potential source of transmissible prezygotic DNA damage.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Detection of benzo[a]pyrene diol epoxide-DNA adducts in embryos from smoking couples: evidence for transmission by spermatozoa.

Tobacco smoking is deleterious to reproduction. Benzo[a]pyrene (B[a]P) is a potent carcinogen in cigarette smoke. Its reactive metabolite induces DNA-adducts, which can cause mutations. We investigated whether B[a]P diol epoxide (BPDE) DNA adducts are detectable in preimplantation embryos in relation to parental smoking. A total of 17 couples were classified by their smoking habits: (i) both partners smoke; (ii) wife non-smoker, husband smokes; and (iii) both partners were non-smokers. Their 27 embryos were exposed to an anti-BPDE monoclonal antibody that recognizes BPDE-DNA adducts. Immunostaining was assessed in each embryo and an intensity score was calculated for embryos in each smoking group. The proportion of blastomeres which stained was higher for embryos of smokers than for non-smokers (0.723 versus 0.310). The mean intensity score was also higher for embryos of smokers (1.40+/-0.28) than for non-smokers (0.38+/-0.14; P = 0.015), but was similar for both types of smoking couples. The mean intensity score was positively correlated with the number of cigarettes smoked by fathers (P = 0.02). Increased mean immunostaining in embryos from smokers, relative to non-smokers, indicates a relationship with parental smoking. The similar levels of immunostaining in embryos from both types of smoking couples suggest that transmission of modified DNA is mainly through spermatozoa. We confirmed paternal transmission of modified DNA by detection of DNA adducts in spermatozoa of a smoker father and his embryo.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

Interovarian differences in levels of cotinine, a major metabolite of nicotine, in women undergoing IVF who are exposed to cigarette smoke.

PURPOSE: Our purpose was to determine whether there is variation in levels of follicular fluid (FF) cotinine between the two ovaries of women undergoing IVF-ET who are exposed to cigarette smoke. METHODS: In 61 women, there were two to four determinations of FF continine levels for each of two follicles, one from each ovary. For each woman a t test for significant difference between the means of both ovaries was done to test for interovarian variation. RESULTS: Thirty-seven nonsmokers, 8 passive smokers, and 16 active smokers differed greatly (P < 0.0001) in mean FF cotinine levels: 13.0, 91.1, and 420.3 ng/ml, respectively. Fourteen women had significant differences, at the P = 0.025 level or below, between their two ovaries. Five of them had differences significant at the 0.001 level. Even so, the correlation between the cotinine levels of the two ovaries was high. CONCLUSIONS: Cotinine uptake between the two ovaries of a woman may differ approximately one-fourth of the time. In spite of these differences, the overall correlation between ovaries is high. The clear distinction in levels of FF cotinine among active, passive, and nonsmokers demonstrates the reliability of FF cotinine testing. Detection of cotinine in a large proportion of nonsmokers shows how pervasive nicotine is in the environment.

Adult↗

Effects of cigarette smoking and age on the maturation of human oocytes.

We investigated whether cigarette smoking, measured by follicular fluid concentrations of cotinine (a major metabolite of nicotine), affects the maturity of oocytes from women undergoing in-vitro fertilization (IVF) and embryo transfer. In 234 women, follicular fluid samples were assessed for cotinine and their 2020 oocytes were assessed for maturity stage. Data on individual proportions of oocytes which were mature (OM) and were fertilized (OF) were analysed by regression in relation to age and follicular fluid cotinine. OF gave an independent assessment of oocyte maturity. Both age and follicular fluid cotinine entered the OM and OF regressions and were significant. The age-adjusted regression coefficients for log cotinine were positive; greater cotinine concentrations usually accompanied greater OM and OF. The cotinine effect on OM was positive in younger women, but it became negative (decreased OM with increasing cotinine concentrations) in older women (> or = 40 years). We further found in older women an average reduction of approximately 50% in the number of mature oocytes; this reduced number was lower than the number of embryos usually transferred. Smoking can reduce the number of mature oocytes even further, therefore risking a negative IVF-embryo transfer outcome. This may be the reason why the negative effects of smoking become clinically detectable in older women.

Adult↗

Cotinine, a major metabolite of nicotine, is detectable in follicular fluids of passive smokers in in vitro fertilization therapy.

OBJECTIVE: To assess cotinine, a metabolite of nicotine, in follicular fluids (FF) of women who smoke either actively or passively or not all. DESIGN: Controlled clinical study. SETTING: Infertile patients in a hospital IVF-ET program. PATIENTS: One hundred eleven women classified by smoking habits: active smokers (n = 44), passive smokers (n = 17), or nonsmokers (n = 50). INTERVENTIONS: Ovarian hyperstimulation. MAIN OUTCOME MEASURE: Cotinine levels in FF. RESULTS: A strong correlation between number of cigarettes smoked and levels of FF cotinine was found. The levels of FF cotinine were: active smokers 710.4 +/- 128.2, passive smokers 76.3 +/- 56.5, and nonsmokers 4.2 +/- 2.0 ng/mL (mean +/- SEM). The level in active smokers was significantly greater than in other groups. The levels of FF cotinine in passive smokers differed significantly from nonsmokers. Eighty-four percent of nonsmokers actually were exposed to nicotine, with a mean value of 5.0 ng/mL. CONCLUSIONS: Cotinine was detectable in a dose-dependent manner in active and passive smokers. It was detected in all active smokers and in a majority of passive smokers and self-reported nonsmokers. A strong interindividual variation suggests differences in metabolism and smoking habits. Follicular fluid cotinine assessments are useful for infertility studies.

Adult↗

Decline in cognitive performance in aging twins. Heritability and biobehavioral predictors from the National Heart, Lung, and Blood Institute Twin Study.

The present study examined the contribution of genetic factors to Digit Symbol performance and its decline in 23 monozygotic twin pairs (mean age at examination 1, 57.1 years) and 21 dizygotic twin pairs (mean age at examination 1, 56.3 years). These men were assessed twice during a 5-year interval as part of the National Heart, Lung, and Blood Institute Twin Study. The prevalence of decline (a change, greater than 1 SD) during the 5-year interval was 35% and 39% for monozygotic and dizygotic twins, respectively. The pairwise concordance for decline was 45% in monozygotic and 8% in dizygotic twin pairs, suggesting a possible role for genetic factors in the decline in Digit Symbol performance in this sample. A comparison of baseline biologic and behavioral characteristics within monozygotic twin pairs discordant for decline in Digit Symbol performance revealed that decliners had higher initial systolic blood pressures, lower serum cholesterol levels, and lower heart rates than nondecliners.

Aged↗

Genetic variation at the immunoglobulin allotype loci in Creoles of Trinidad.

The sera of a sample of 204 Creoles from Trinidad were tested for the presence of polymorphic gene complexes occurring on immunoglobulin light- and heavy-chain molecules including the allotypic markers IGKC 1, IGHA2 1 and 2, IGHG1 A, X, F, and Z, and IGHG3 G, G5, B0, B1, B3, B4, B5, C3, C5, S, and T. Nine IGHG (GM) haplotypes occur in polymorphic frequencies (greater than .01) in this population, including known African, Asian, Caucasian, and Amerindian marker haplotypes. Significant differences (P less than .01) were found in the frequency distributions of three IGHG (GM) haplotypes and the frequency of IGKC*1 in these data and data from Creole populations of Belize and St. Vincent. The Creoles of Trinidad and St. Vincent are more similar in IGHG (GM) haplotype distributions than are Trinidad and Belize populations. Previous testing has revealed no significant differences between St. Vincent and Belize Creoles at the Ig allotypic loci. Analysis of migration patterns in the Caribbean suggests that different rates of Asian migration have maintained regional diversity at these loci, while continuous gene flow from the eastern Caribbean to Trinidad has had a relative homogenizing effect on the gene pools of this area.

Chi-Square Distribution↗

Sperm from some infertile men may consist of several populations.

In the hamster ovum penetration (HOP) test, when ova have equal penetrability and sperm have equal penetrating ability, the distribution of zona-free hamster ova classified by number of penetrating human sperm is expected to follow the Poisson distribution (PD). This study reports tests for PD in HOP tests on 9 infertile patients and 11 normal controls. The data, presented in detail, show the expected PD in the control group. In contrast, 3 patients had HOP tests with definite non-PDs, whereas 5 patients have clearcut PDs. The cause of non-PD is unknown, but could result from differences among motile sperm in penetrating ability.

Adult↗

Confirmation of an abnormal (non-Poisson) distribution of sperm from some infertile men in the hamster-ovum test.

The present study was carried out to investigate an earlier report that stated that some men of infertile couples (patients), but not normal donors, have an abnormal (non-Poison) distribution of penetrating sperm among ova in the hamster-ovum test. Semen samples from 60 men, 24 proven fathers and 36 patients, were analyzed for agreement with the theoretical Poisson distribution (PD). Most of the fathers (23 of 24) fit PD well, but 10 of the patients did not. The overall (group) fit of fathers is good, but that of the patients is poor. Patients, but not fathers, are heterogeneous in their agreement with PD; about 25% fit poorly whereas more than 50% fit well. The 25% fitting poorly may often be those patients who are truly infertile (even when their wives are actually fertile).

Adult↗

Similarities and differences in acute cardiovascular responses to alcohol among normal men of European, Japanese, and Chinese ancestry: a univariate and multivariate analysis.

Normal young adult males residing in Hawaii (46 of European ancestry, 30 Japanese, 27 Chinese) were tested for changes in heart rate and blood pressure following a dose of 0.59 g of ethanol/kg. The two Oriental groups did not differ in mean changes but, when pooled, differed from Europeans, having increased heart rate and decreased blood pressure. Within-race analyses showed that, contrary to the literature, all three groups have great interindividual differences in cardiovascular responses. In addition, the three races show a basically similar multivariate response: blood pressure more variable than heart rate and blood pressure changes uncorrelated with heart rate changes.

Adult↗

Variability in serologically detected male antigen titer and some resulting problems: a critical review.

Seroologically detected male antigen" (also called H-Y antigen) was first described in normal male mammals but now appears to occur in normal female mammals as well. "Serologically detected male predominant" (SDMP) antigen is a more appropriate name since the titer in normal males usually exceeds that of normal females. As we show, in each sex there is a considerable inter-individual variability in SDMP antigen titer, and in moderate-to-large size samples the low end of the male range of titers usually coincides with the high end of the female range. Several major problems arise from failure to recognize and/or to deal adequately with this normal variation in SDMP antigen titer. The chief problem is that the "controls" used (often a single individual) may be inadequate and misleading, leading to unjustified designation of samples as "positive", "negative", or even "deviant" ("intermediate", "reduced") for SDMP antigen titer. Other problems include deficiencies in technique and lack of statistical control for test and sample variability. Adequate attention to these problems, especially to the normal variability in SDMP antigen titer, could reduce the contradictions and inconsistencies which have troubled this field.

Animals↗