Sister chromatid exchanges and dementia of the Alzheimer type.

Sister chromatid exchange (SCE) analysis was carried out on ten patients with the clinical diagnosis of dementia of the Alzheimer type (DAT) and 11 cognitively-intact controls of a comparable age. There was no significant difference between patient and control groups in either the mean baseline SCE frequency or the SCE frequency following in vitro exposure to mitomycin-C. The present results, based on the largest sample (n = 21) published to date, fail to confirm the single positive report in the literature of an increased baseline SCE frequency in DAT patients compared to controls.

Philothermal response, microtubules and dementia.

The role of microtubules in the philothermal response of polymorphonuclear leukocytes (PMNs) was examined using colchicine, a known microtubule disrupting agent. Colchicine inhibited PMN migration in a dose dependent fashion. Spatial distribution analysis of the responding cell population revealed a preferential inhibition of distal cell migration, a pattern similar to that found for PMNs obtained from patients with dementia of the Alzheimer type (DAT). The result is consistent with the known role of microtubules in directed cell migration and the hypothesized microtubular defect in DAT. Further investigations of microtubules may provide insight into the etiology and pathogenesis of DAT.

Philothermal and chemotactic locomotion of leukocytes. Method and results.

A newly developed technique for quantitating the locomotion of polymorphonuclear leukocyte (PMN) populations in temperature gradients has revealed that PMNs accumulate toward higher temperatures. The experiments yield measurements of the numbers of cells that adhere to glass and migrate from a cell suspension through a liquid/gel meniscus into a glass/agarose interface, and of their spatial distribution at subsequent time intervals. Cell locomotion was investigated as a function of the magnitude, sign, and temporal variation of the temperature gradient, the cell concentration in the source suspension, and the presence or absence of chemoattractant gradients. It was found (1) that a temperature gradient stimulates crossing of the meniscus toward higher temperatures, (2) that only a portion of the cells reverses direction of locomotion in response to reversal of the temperature gradient after the cells have traversed the meniscus, and (3) that the distribution of cells in the migration space depends on cell concentration, suggesting that the dynamics of PMN locomotion depend on cell-cell interactions.

Philothermal response of polymorphonuclear leukocytes in dementia of the Alzheimer type.

The philothermal response, i.e., the tendency of polymorphonuclear leukocytes (PMNs) to migrate along a temperature gradient toward warmer temperatures, was evaluated in 11 patients with a clinical diagnosis of dementia of the Alzheimer type (DAT) and compared to 11 age and sex-matched mentally normal individuals. While the total number of migrating PMNs did not differ significantly between these two groups, there was a significant difference in the spatial distribution of the responding cell population. The numerical parameter, R, has been introduced to provide a quantitative measure of the distribution of populations characterized by differences in motile behavior. This R value was unusually high for 10 of the DAT patients but only one of the comparison individuals. No relation between R and duration of illness, age, or sex was detected. These preliminary findings, based on a small number of clinically diagnosed DAT patients, suggest that the philothermal response may represent a biological marker with diagnostic usefulness for at least one subgroup of DAT patients.

In vivo cytogenetic effects of cannabinoids.

The cytogenetic effects of subacute oral administration of delta-9-tetrahydrocannabinol, cannabidiol, cannabinol, and placebo were assessed in 27 subjects in a prospective double-blind study. Both conventional chromosome aberration analysis and sister chromatid exchange were considered. A comparison group of 5 nondrug users was also investigated. The aneuploidy frequency decreased significantly following delta-9-tetrahydrocannabinol administration. By contrast, the frequencies of chromosome aberrations increased slightly for all three drug groups and decreased in the placebo and comparison groups although none of the predrug versus postdrug comparisons were statistically significant. No increase in the sister chromatid exchange frequency was found in any of the groups when predrug versus postdrug comparisons were made. The present study is the fourth short term prospective investigation failing to demonstrate a statistically significant increase in chromosome damage due to cannabinoid usage. However, it must be kept in mind that to date only gross chromosomal aberrations have been identified so that the more subtle chromosomal as well as molecular genetic damage has not been ruled out.

Chromosomes in patients receiving methadone and methadyl acetate.

Chromosomes of peripheral leukocytes were examined in 28 addicts participating in a Veterans Administration-Special Action Office for Drug Abuse Prevention (SAODAP) cooperative study of methadyl acetate vs methadone. Blood samples for 72-hour leukocyte cultures were drawn after nearly 40 weeks of maintenance therapy while subjects were receiving active medication. For comparison, ten nondrug users were also studied. The frequency of chromosome damage was not greater in subjects maintained on methadyl acetate or methadone than in nondrug users.

In vitro effects of imipramine on proliferation of human leukocytes.

The effects of imipramine hydrochloride on cell proliferation were investigated in leukocyte cultures derived from normal volunteers. Nine different doses of imipramine were added in vitro at random for 4, 24, 48, and 68 hours, the three lowest concentrations being within the range of plasma levels reported in psychiatric patients receiving the drug therapeutically. Cell proliferations, as measured by mitotic index, was affected by both the concentration and the duration of drug exposure; the higher the dose and/or the longer the drug in culture, the lower the mitotic index. Imipramine concentrations corresponding to therapeutic plasma levels had no effect on mitotic index regardless of the length of exposure.

Marijuana exposure in vivo and human lymphocyte chromosomes.

Sequential chromosome examinations of peripheral lymphocte cultures were carried out on 21 adult male volunteers who smoked natural blend marijuana cigarettes containing about 1%, 2%, or no delta9-THC. For a limited number of subjects, blood samples from a single venipuncture were cultured independently in two cytogenetic laboratories, and later the slides were exchaged for re-analysis. There were significant differences between laboratories in the absolute break frequencies recorded. These inter-laboratory differences were demonstrated for both techniques of cell culture and metaphase analysis. Neither laboratory found a statistically significant increase in break frequencies asssociated with marijuana smoking. The present study, therefore, failed to detect a measurable effect of marijuana smoking on chromosomal aberrations in subjects experienced in the use of the drug.

The in vitro effects of imipramine on human chromosomes.

The clastogenic effects of imipramine on chromosomes have been investigated in leukocyte cultures from seven healthy blood donors (2 mlae and 5 female), repeat cultures being initiated at intervals of 6 to 12 weeks. At various times prior to harvesting nine different doses of imipramine were added in vitro, the three lowest concentrations being within the range of plasma levels reported in psychiatric patients reveiving the drug therapeutically. In addition, streptonigrin was used as a positive control. No increase in chromosome breaks was found at any concentration for any duration of exposure even in those cultures where high concentration and/or long duration of exposure significantly suppressed cell growth. Only cultures to which streptonigrin had been added showed a significant increase in chromosome breaks.

Chromosomes in old age: a six year longitudinal study.

This first longitudinal study on aged subjects confirms previous cross-sectional observations of increasing aneuploidy with advancing age in women but not in men. In this study of 17 aged twins (mean age 89.7 years), 11 women and 6 men, spanning an interval of approximately 6 years between examinations, only women showed a significant increase in hypodiploidy (also hyperdiploidy and monosomy C). This increase in hypodiploidy was not due to a high frequency of chromosome loss in a few subjects but rather was exhibited by most of the subjects. While men showed a loss in G-group chromosomes during this 6-year interval, that loss was not statistically significant. These findings confirm for the first time by means of longitudinal follow-up that women and not men, even in the ninth decade of life, show a significant increase in hypodiploidy.

The Relationship between Chiasmata and Crossing over in TRITICUM AESTIVUM.

Telocentrics for the beta arm of chromosome 4A and the long arm of 6B were used as cytological markers for the determination of chiasma frequency. In concomitant studies of recombination, terminal segments of rye and T. umbellulatum chromatin carrying Hp (Hairy peduncle) and Lr9 (Leaf-rust resistance), respectively, marked 4A and 6B. Two temperatures, 21 degrees and 32 degrees , were used for both the 4A and 6B experiments.-Only one chiasma was observed in each heteromorphic bivalent. Because there was a substantial reduction in pairing between diakinesis and metaphase I, all determinations of chiasma frequency were made at diakinesis. In the 21 degrees experiments, agreement was good between genetic recombination and cytological prediction on the basis of the partial chiasmatypy hypothesis that each chiasma represents a crossover. At 32 degrees both chiasma frequency and crossing over, but particularly the latter, were strongly reduced. The fewer crossovers than expected are explained in part by stickiness of chromosomes at the high temperature, sometimes resulting in adjacent chromosomes being wrongly scored as having a chiasma, and in part by premetaphase disjunction of some recombined bivalents and subsequent independent behavior of the two resulting univalents.-Male transmission of the 4A telocentric from the heteromorphic bivalent was unusually high: 51% at 21 degrees and 31% at 32 degrees .