Measurement of Compton scattering from the deuteron and an improved extraction of the neutron electromagnetic polarizabilities.

The electromagnetic polarizabilities of the nucleon are fundamental properties that describe its response to external electric and magnetic fields. They can be extracted from Compton-scattering data-and have been, with good accuracy, in the case of the proton. In contradistinction, information for the neutron requires the use of Compton scattering from nuclear targets. Here, we report a new measurement of elastic photon scattering from deuterium using quasimonoenergetic tagged photons at the MAX IV Laboratory in Lund, Sweden. These first new data in more than a decade effectively double the world data set. Their energy range overlaps with previous experiments and extends it by 20 MeV to higher energies. An analysis using chiral effective field theory with dynamical Δ(1232) degrees of freedom shows the data are consistent with and within the world data set. After demonstrating that the fit is consistent with the Baldin sum rule, extracting values for the isoscalar nucleon polarizabilities, and combining them with a recent result for the proton, we obtain the neutron polarizabilities as αn=[11.55±1.25(stat)±0.2(BSR)±0.8(th)]×10(-4) fm(3) and ßn=[3.65∓1.25(stat)±0.2(BSR)∓0.8(th)]×10(-4) fm(3), with χ(2)=45.2 for 44 degrees of freedom.

First measurements of spin-dependent double-differential cross sections and the Gerasimov-Drell-Hearn Integrand from 3He(γ,n)pp at incident photon energies of 12.8 and 14.7 MeV.

The first measurement of the three-body photodisintegration of longitudinally polarized (3)He with a circularly polarized γ-ray beam was carried out at the High Intensity γ-ray Source facility located at Triangle Universities Nuclear Laboratory. The spin-dependent double-differential cross sections and the contributions from the three-body photodisintegration to the (3)He Gerasimov-Drell-Hearn integrand are presented and compared with state-of-the-art three-body calculations at the incident photon energies of 12.8 and 14.7 MeV. The data reveal the importance of including the Coulomb interaction between protons in three-body calculations.

Protection against Adriamycin cytotoxicity and inhibition of DNA topoisomerase II activity by 3,4-dihydroxybenzoic acid.

The mechanism of Adriamycin (ADR) induced cytotoxicity is not completely understood. While a variety of mechanisms have been proposed, the production of free radicals by redox cycling of the semiquinone has been implicated in cytotoxicity, specifically for cardiotoxicity. To determine whether a scavenger of free radicals would modify the cytotoxicity of ADR, the benzoic acid derivative 3,4-dihydroxybenzoic acid (DHB) was investigated for its ability to protect against ADR-induced cytotoxicity and DNA double strand breaks in Chinese hamster V79 cells. V79 cells were treated with ADR, or its non-redox cycling analog iminodaunomycin, in the presence or absence of DHB. DHB provided significant protection (dose-modifying factor greater than 2.5 for ADR, and nearly 2 for iminodaunomycin) and also caused a dose-dependent decrease in DNA double strand breaks as measured by pulsed field gel electrophoresis. Assays of topoisomerase II activity showed that DHB inhibited topoisomerase II in a concentration-dependent manner, but did not inhibit topoisomerase I. Another non-toxic topoisomerase II inhibitor, the radioprotector WR-1065, also protected against ADR-induced cytotoxicity. These data identify DHB as a non-toxic inhibitor of DNA topoisomerase II and suggest that much of the cytotoxicity of ADR in actively growing V79 cells is due to mechanisms other than redox cycling by the semiquinone.

Methodological review and meta-analysis of sexuality and menopause research.

A selection of empirical studies from 1972-1992 that assessed sexuality and the peri/post menopausal women were collected and reviewed. Using a blind procedure, two Ph. D. experimental psychologists rated methodology sections of all studies. For comparison, variables that were related to peri/postmenopausal sexuality were converted to a standard effect size and correlation. Significantly higher effects sizes were found in studies that were rated as having an adequate measure of hormone status or adequate hormone manipulation, included appropriate controls, and had less confounding variables. Larger effect sizes tended to be found for studies that had an adequate measure of sexuality. Ratings of representativeness of the population, number of subjects, age of the subjects, adequacy of the menopause measure or statistical analysis were not related to effect sizes. Multiple regression analysis showed that overall ratings accounted for 31% of the variance of effect sizes. For studies in which an effect size could be calculated a mean D of 0.67 +/- 1.23 (SD) was found indicating that hormones, both exogenous and endogenous, have some importance to peri/postmenopausal sexuality. Difficulties encountered in attempting a meta-analysis in this area and the meaning of the findings are discussed, as is the importance of such an analysis to the area of sexuality and menopause research.

Energy and charge localization in irradiated DNA.

The relation between the site of energy deposition and the site of its biological action is an important question in radiobiology. Even at 77 degrees K, evidence is clear that these two sites must be separated since energy deposition is random but specific products are formed. Several processes that may contribute to this separation are: 1) hole migration and stabilization through deprotonation to give neutral oxidation product radicals; 2) electron trapping and transfer to form specific radical anions, possibly followed by protonation to give neutral reduction product radicals; and 3) recombination of spatially separated charges or radicals. These microscopic processes will be reviewed critically in an analysis using electron paramagnetic resonance spectroscopy (EPR) evidence for and against long-range transfer of energy and/or charge in frozen, hydrated DNA.

Radiation chemistry of the hippocampal brain slice.

The in vitro hippocampal brain slice is a 0.4 mm thick neural network that can be used to study brain responses to radiation and related injuries. This preparation is unique in that it responds to ionizing radiation within minutes after exposure without complications from changes in vascularity, blood flow, blood pressure, etc. Electrophysiological studies have shown that x- and gamma-rays alter synaptic transmission and spike generation, elements of normal brain activity. To evaluate the role of hydroxyl free radicals (OH) in these changes, slices were exposed to dilute H2O2 solutions. EPR spin trapping experiments verified that OH is produced. Neural responses, while similar, were not identical to those due to radiation, possibly because of a different distribution of OH. Although H2O2 is freely diffusible, it produces OH at specific sites where, e.g. iron reduces it. In contrast, x- and gamma-rays produce OH more uniformly throughout the tissue. H2O2 may provide a better model for high-LET radiation where yields of radical products of water radiolysis are decreased and peroxide reactions predominate.

Drug attitude factors: comparisons of samples from 1985 and 1992.

The Stanislaus Chemical Effects Survey, which contains the names of twenty-four substances and asks subjects to rate the relative harm and benefit of each to society, was given to male and female undergraduates in 1985 and 1992. Factor analysis of the responses from each sample were done separately and then a comparison was made of the resulting factors. Fifteen of the twenty-four drugs retained their approximate same position in the structure of drug attitudes between the two samples. Attitudes about three substances, tobacco, oral contraceptives, and PCP, notably appeared to have undergone significant shifts. Discriminant analysis revealed significant differences between the two samples, between males and females regardless of year, and an interaction between year and gender. Findings suggest that attitudes remain conservative about drugs in general and that public policies may be contributing to the shifts in attitudes seen.

The brain renin-angiotensin system and prolactin secretion in the male rat.

The present studies investigated the role of the brain renin-angiotensin system in the regulation of PRL secretion in the male rat. Blood samples were taken from conscious rats before, during, and after administration of test substances into the third cerebral ventricle. In the first series of experiments, we determined the sensitivity of the PRL response to intracerebroventricular (icv) administration of angiotensin II (Ang II) and found that PRL levels were significantly suppressed in a dose-related manner (10-500 ng). A dose of 1 ng did not significantly affect PRL values, compared to those from vehicle-injected animals. Ang II elicited water intake at doses of 50 and 500 ng, but not at the 10- or 1-ng doses. In the second series of experiments, we investigated the role of endogenous brain Ang II in the regulation of PRL secretion under basal and stimulated conditions. The endogenous system was manipulated by icv infusion of saralasin, an Ang II receptor antagonist, or icv injection of enalaprilat, a converting enzyme inhibitor, to prevent synthesis of Ang II. Neither saralasin nor enalaprilat administration produced an increase in PRL levels under basal, nonstressed conditions. However, during immobilization stress, when PRL levels increased 3-fold during icv vehicle infusion, saralasin infusion resulted in a 7-fold rise in plasma PRL titers relative to prestress baseline values. These results demonstrate that, in male rats, the inhibitory effects of icv administration of Ang II on PRL secretion are very sensitive and are observed at doses which do not affect water intake. The endogenous brain Ang II system appears not to be involved in the maintenance of the low plasma PRL levels observed under basal, nonstressed conditions. However, the system does appear to affect the magnitude of the PRL response to immobilization stress.

Effects of estrogen, androgen, and progestin on sexual psychophysiology and behavior in postmenopausal women.

To assess the contribution of gonadal steroids to sexual behavior in aging women, we conducted a 10-week, double-blind, hormone replacement study of 40 naturally menopausal women (mean age, 58.3 yr). Prospective measurements of basal and stimulated vaginal vasocongestion and daily self-reports of mood, physical symptoms, sexual behavior, and perceived sexual pleasure were collected. Daily treatments were either conjugated equine estrogen, i.e. Premarin (P; 0.625 mg), Premarin and medroxyprogesterone acetate, i.e. Provera (PP; 0.625 and 5 mg, respectively), Premarin and methyltestosterone (PT; 0.625 and 5 mg, respectively), or placebo (PL). Compared to placebo, hormone treatment had significantly reduced hot flashes in the P and PP groups by week 4 and in the PT group by week 5. Headaches were reduced in the P vs. PL group, only. Hormone treatment did not significantly alter mood ratings, sexual behaviors, or psychophysiologically measured sexual arousal. PT treatment significantly increased reports of pleasure from masturbation compared to the other three groups, underscoring the apparent contribution of androgens to self-stimulatory behavior. However, the data suggest that in these physically and sexually healthy women, gonadal steroids do not influence major components of sexual functioning, including arousal and a wide variety of sexual activity and experience.

In vivo studies on paracrine actions of pituitary angiotensin II in stimulating prolactin release in rats.

The present experiments were performed to test the hypothesis that, in vivo, intrapituitary angiotensin II (ANG II) mediates the effect of luteinizing hormone-releasing hormone (LHRH) on prolactin release. After intravenous administration of LHRH (100 ng/100 microliters saline), plasma levels of both luteinizing hormone (LH) and prolactin were increased in ovariectomized rats pretreated with estradiol and progesterone. Intravenous administration of saralasin or sarthran (ANG II receptor blockers) reduced or abolished, respectively, the LHRH-induced increase in prolactin without affecting the rise in LH. In other ovariectomized steroid-treated rats, saralasin did not affect the increase in LH or prolactin induced by 10 min of restraint stress. Finally, in intact female rats on the day of proestrus, neither saralasin nor sarthran affected the mid-cycle prolactin surge. Taken together, these results show that in vivo exogenous LHRH stimulates prolactin release via a paracrine action of pituitary ANG II. However, under other conditions in which both LH and prolactin (and presumably endogenous LHRH) are elevated, pituitary ANG II does not appear to be involved in the prolactin rise.

The brain Renin-Angiotensin system and the regulation of prolactin secretion in female rats: influence of ovarian hormones.

Abstract This study was designed to investigate the effects of exogenous and endogenous angiotensin II (All) on prolactin release in ovariectomized rats, with and without estrogen and progesterone pretreatment. In the first series of experiments, All or vehicle was injected into the third cerebral ventricle of conscious, freely-moving rats. In both treated and untreated rats, administration of 50 ng All suppressed prolactin levels within 15min of injection, compared to vehicle-injected rats. In untreated rats, prolactin levels returned to baseline values by 30 min, while in treated rats, prolactin levels remained suppressed for an hour. In the second series of experiments, the involvement of endogenous brain All in tonically suppressing prolactin release was assessed by administering either All receptor blockers (saralasin or sarthran) or an All synthesis inhibitor (enalaprilat, an inhibitor of the conversion of angiotensin I to All). Neither All receptor blockade nor converting enzyme inhibition resulted in any change in prolactin levels in untreated levels in untreated rats. However, following treatment with ovarian steroids, infusion of saralasin or injection of enalaprilat resulted in a significant increase in plasma prolactin tilers. During saralasin infusion, prolactin levels were significantly increased by 15 min and continued to be higher than controls at 60 min. After enalaprilat administration, prolactin levels did not rise significantly until 90 min and then remained elevated up to 120 min post-injection. These latter results suggest that at least one h is required for maximal inhibition of angiotensin synthesis in the brain. These data demonstrate that low doses of All suppressed basal prolactin secretion in both untreated and ovarian steroid-treated, ovariectomized rats. However, treated rats appeared to be more sensitive than untreated animals to the prolactin-lowering effects of centrally administered All. The lack of prolactin response in untreated rats when brain All synthesis was inhibited or All receptors were blocked suggests that, in the absence of ovarian steroids, endogenous All was not acting tonically to suppress prolactin secretion. Following exposure to ovarian steroids, however, the endogenous brain All system appeared to be activated and involved in controlling prolactin release.

Effectiveness of a procedure for disinfecting the vaginal photoplethysmograph contaminated with herpes simplex virus type 2.

To test the effectiveness of a disinfecting procedure involving 2% glutaraldehyde, a vaginal photoplethysmograph was contaminated with a known amount of herpes simplex type 2 (HSV-2). The vaginal photoplethysmograph was then put through the disinfection procedure. Two virus solutions were tested, one designed to approximate the concentration found in a naturally occurring infection (low inoculum), the other with 100 times more virus (high inoculum). Varying lengths of exposure to glutaraldehyde were tested. Results of assays for the virus after the device was disinfected showed that no measurable infectious virus remained even at the shortest exposure to glutaraldehyde, 1 min. A second experiment was conducted in which glutaraldehyde was added directly to a virus solution. Results confirmed those of the first experiment.

Stochastic model of free radical yields in oriented DNA exposed to densely ionizing radiation at 77K.

Monte Carlo simulation techniques were used to calculate the probability that thymine radical anions (T.-), formed by the slowing-down of high-energy protons in oriented DNA, will undergo a secondary protonation reaction. By assuming a large asymmetry in the thermal conductivity of oriented DNA fibres we predict a significant enhancement of protonation of T.- when the proton flux is incident on the sample parallel to the orientation of the DNA. These results are in qualitative agreement with experimental data on the production of TH. radicals when oriented DNA is exposed to fast neutrons.

Neutron-induced free radicals in oriented DNA.

Samples of oriented DNA containing 30 per cent water were irradiated with neutrons at 77 K. The electron spin resonance (e.s.r.) spectra obtained from these irradiated DNA samples show that the formation of radicals is different when the incident neutrons are parallel or perpendicular to the DNA helix. When the incident neutrons are perpendicular to the DNA helix the e.s.r. spectra of thymine and guanine ionic radicals (T-., G+.) are observed. An additional e.s.r. spectrum corresponding to the hydrogen addition radical on thymine (TH.) is observed when the incident neutrons are parallel to DNA helix. The TH. radical appears to be formed by protonation of T-. .

DNA repair synthesis in minimally stressed human lymphocytes.

We have estimated the rate of unscheduled DNA synthesis (UDS) in human lymphocytes from measurements of tritiated thymidine incorporation into double-stranded DNA (ds-DNA) during incubation of cells in vitro. Cells were not subjected to stresses except those associated with careful handling, or in certain experiments, mild heating or treatment with phytohaemagglutinin (PHA). Contribution of scheduled DNA synthesis (SDS) to incorporation was reduced by inhibiting replication and separating freshly replicated single-stranded DNA from repaired ds-DNA by chromatography. By increasing the incubation temperature, which decreases SDS and increases UDS, the residual contribution of scheduled DNA synthesis to thymidine incorporation into ds-DNA was estimated. Effects of increasing the number of cells in S-phase by phytohaemagglutinin were also investigated. Results suggest that: the rate of unscheduled DNA synthesis is about 500 +/- 100 thymidine molecules incorporated per cell per hour; a temperature-sensitive process, probably hydrolysis of DNA, contributes much of the damage repaired by UDS; background ionizing radiation contributes little to the damage; and damage caused by DNA hydrolysis is repaired much more efficiently than lethal damage caused by ionizing radiation. Large increases in incorporation into ds-DNA occurred when cells were stimulated with PHA.