T. Edward Reed

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.

Conduction Velocity in a Brain Nerve Pathway of Normal Adults Correlates with Intelligence Level.

Abstract This is a detailed report of the first demonstration in normal individuals of a correlation between intelligence level (“IQ”) and nerve conduction velocity (NCV) in a brain nerve pathway. A total of 147 postsecondary students were tested for nonverbal IQ and latency of the P100 (a visually evoked potential recorded over the primary visual cortex); this latency was used to estimate an approximate NCV in the visual pathway (retina to visual cortex). The correlation between this NCV and IQ is + .26 (p = .002); after correction for the restricted IQ range (but not for rest ceiling or attenuation), + .37. Three recent studies of mentally retarded patients, using similar stimulation and recording, also showed increased P100 latencies relative to controls. These results, plus those of other IQ studies using choice reaction time or long-latency evoked potentials, are all explainable by positive correlations between brain NCV and speed of information processing and between this speed and intelligence level.

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.

Arm nerve conduction velocity (NCV), brain NCV, reaction time, and intelligence ☆

Abstract Two hundred California students, 18 to 25 years old, were tested for nerve conduction velocity (NCV) in the arm and in the visual pathway of the brain, simple and choice reaction times, and Ravens Progressive Matrices test for nonverbal intelligence. Contrary to a prediction based on theoretical grounds, and also to one study, arm NCV did not correlate with this intelligence measure. It also did not correlate consistently with the brain NCVs or with reaction time. In contrast, these brain NCVs do correlate positively (as predicted) with this measure of intelligence in this group of subjects and also in each of five electrophysiological studies of mentally retarded or demented subjects (relative to normal controls). A correct interpretation of these results should assist our understanding of the neurophysiological basis for human information processing and intelligence.

Sex difference in brain nerve conduction velocity in normal humans

Nerve conduction velocity (NCV), the speed at which impulses travel along nerves, has been extensively determined in human peripheral nerves because of its clinical utility. In contrast, almost no studies have been made of human brain NCV. We determined brain NCVs in the visual nerve pathway for 185 male and 200 female university students ages 18-25 years. In each of three independent test conditions, we found that the mean NCV of male students is about 4% faster than in females (P < or = 0.0001 for each condition). These male students also have a shorter reaction time in each of seven different RT tests than do females, even though, on the null hypothesis of equal NCVs, we would expect males to have longer RT times because of their greater physical size. Four of these comparisons are significant at or below the 0.001 level. These males also increase their NCVs with increasing age, in contrast to females. These sex differences in NCV parallel reported sex differences in age changes in white matter in the brain. These age changes may largely explain these NCV differences.

Choice Reaction Time and Visual Pathway Nerve Conduction Velocity Both Correlate With Intelligence but Appear Not to Correlate With Each Other: Implications for Information Processing

Reed and Jensen (1992) studied 147 normal young adults and reported a significant positive correlation between nerve conduction velocity (NCV) in a brain nerve pathway (V:P100) and a measure of nonverbal IQ, in agreement with clinical studies. It was argued that V:P100 is a useful approximation to cortical NCV, should affect the speed of information processing (SIP), and so, should be a factor affecting IQ. In this article the choice and simple reaction times (CRT and SRT) and their differences, in the same subjects, were examined. Individual discriminative (Oddman) RT (ODRT) minus SRT (ODRT - SRT), which is the actual “cognitive time,” correlated highest with IQ: r = −.23, p = .005. CRT is also a measure of SIP so V:P100 and ODRT - SRT are expected to correlate with each other. In these 147 subjects, however, they cannot be shown to be correlated (r = .044, p = .60; absolute true value probably < .20). This suggests that (1) there are two largely independent neurophysiological processes affecting normal intelligence, and (2) the differences among normal subjects in CRT are not entirely due to differences in mean cortical NCV. Recent electrophysiological data indicate that normal persons can have different patterns of neural connectivity among cortical regions during a visuomotor task requiring decision. Consequently, the simplest interpretation of the great ODRT -SRT variability observed among our subjects is that it reflects different total lengths of cortical pathway involved in the ODRT task, more intelligent subjects having shorter path lengths on average than less intelligent subjects. This interpretation can also explain the reported lower brain energy requirement of more intelligent persons for doing a specified mental task.

A possible major contribution to mental retardation in the general population by the gene for microcephaly

In a study of 13 families with genetic microcephaly, it was found that 11 of 24 parents (two fathers not ascertained) and 11 of 33 non‐microcephalic siblings were of subnormal intelligence. In a rare autosomal recessive condition, all parents and two‐thirds of unaffected siblings are presumed carriers of the gene. It so, nearly 50% of all presumed heterozygotes in the present study were mentally retarded. This proportion agrees well with the other major study of microcephaly in North America, but differs from the Dutch study. On the basis of pooled data from the three studies and the estimated incidence of 1:40000 for genetic microcephaly, it is postulated that (1) about 0.34% of the general population is mentally retarded because it is carrying the gene for microcephaly and (2) about one of nine mentally retarded individuals is heterozygous for the gene for microcephaly.

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

Summary“Serologically 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.

Simple Reaction Time as a Suppressor Variable in the Chronometric Study of Intelligence.

Individual differences in reaction time (RT) to various elementary cognitive tasks (ECTs) reflect variance in both peripheral (sensorimotor) and central components of information processing. Minimizing the variance associated with peripheral processes by controlling simple RT in chronometric studies of more complex ECTs involving choice, discrimination, memory scanning, or other central processes, can increase the correlation between RTs and scores on complex psychometric tests of ability, thereby identifying more clearly the elementary processes involved in psychometric g and other abilities. Simple RT can be controlled by subtraction, partial correlation, and multiple correlation. The relative effectiveness of the different methods depends on various features of the chronometric data. The methods are explicated, with examples from a study of simple, choice, and discriminative RTs (the odd man out paradigm) in 213 male students from three colleges.

Narrow-sense heritability estimates for nerve conduction velocity and residual latency in mice

Conduction velocity (CV) and residual latency (RL; delay at the neuromuscular junction) were determined in the tail nerves of 1366 HS mice distributed in 230 families. The mean CV was 25.76 m/s, with a range from 17.44 to 34.62 m/s. The mean RL was .93 ms, with a range from .63 to 1.32 ms. Estimates of narrow-sense heritabilities (hn2) were obtained by regressing midoffspring means on midparent means. Thehn2 estimate for CV was .228±.053 (p<.0001); that for RL was .069±.053 (p=.20). The CV estimate agrees with previous estimates from mice; reasons are given whyhn2 in humans should be appreciably greater. Since human intelligence appears to be correlated with information processing speed, and brain CV should be a component of this speed, CV may have some important implications for intelligence.