Combined role of childhood maltreatment, family history, and gender in the risk for alcohol dependence.

BACKGROUND: Studies of the relationship between childhood maltreatment and alcohol dependence have not controlled comprehensively for potential confounding by co-occurring maltreatments and other childhood trauma, or determined whether parental history of alcohol disorders operates synergistically with gender and maltreatment to produce alcohol dependence. We addressed these issues using national data. Method Face-to-face surveys of 27 712 adult participants in a national survey. RESULTS: Childhood physical, emotional and sexual abuse, and physical neglect were associated with alcohol dependence (p<0.001), controlling for demographics, co-occurring maltreatments and other childhood trauma. Attributable proportions (APs) due to interaction between each maltreatment and parental history revealed significant synergistic relationships for physical abuse in the entire sample, and for sexual abuse and emotional neglect in women (APs, 0.21, 0.31, 0.26 respectively), indicating that the odds of alcohol dependence given both parental history and these maltreatments were significantly higher than the additive effect of each alone (p<0.05). CONCLUSIONS: Childhood maltreatments independently increased the risk of alcohol dependence. Importantly, results suggest a synergistic role of parental alcoholism: the effect of physical abuse on alcohol dependence may depend on parental history, while the effects of sexual abuse and emotional neglect may depend on parental history among women. Findings underscore the importance of early identification and prevention, particularly among those with a family history, and could guide genetic research and intervention development, e.g. programs to reduce the burden of childhood maltreatment may benefit from addressing the negative long-term effects of maltreatments, including potential alcohol problems, across a broad range of childhood environments.

Histology and chimeral segregation reveal cell-specific differences in the competence for shoot regeneration and Agrobacterium-mediated transformation in Kohleria internode explants.

Internode explants of Kohleria sp. (Gesneriaceae) are capable of regenerating large numbers of adventitious shoots. Regeneration of green shoots from explants of an albino periclinal chimera with genetically green L1, as well as microsurgical removal of the epidermis revealed that shoots originate only from the epidermis. Histological studies further showed that shoots arise from a particular epidermal cell type, viz the basal cell of young glandular trichomes. On the other hand, cells competent for Agrobacterium-mediated transformation are mainly located in vascular tissues, as could be shown by histochemical localization of ß-glucuronidase (GUS) expression in explants that had been inoculated with A. tumefaciens strains carrying binary plasmids with GUS and kanamycin resistance (NPTII) genes. Only 3% of GUS expression events took place in the epidermis. Consequently, shoot regeneration in the presence of kanamycin was very poor. Moreover, most of those shoots proved GUS-negative and did not survive subcultivation on kanamycin-containing medium. Six regenerants, however, were most probably transgenic, as suggested by the ability to produce adventitious shoots in the presence of kanamycin and by polymerase chain reaction (PCR) analysis. To our knowledge, this is the first positive result towards genetic transformation in a taxon of the Gesneriaceae.

High Uniformity of plants regenerated from cytogenetically variable embryogenic suspension cultures of poinsettia (Euphorbia pulcherrima Willd. ex Klotzsch).

Shoot tip explants, callus and embryogenic cell suspensions of Euphorbia pulcherrima have been examined for quantitative variation in nuclear DNA content by means of cytophotometry. Increasing instability was found in calli and cell suspensions from Erlenmeyer flask and bioreactor culture. Nuclear DNA content ranged from 2C up to 32 C. Plants regenerated from embryogenic cell suspensions, however, were highly uniform with regard to phenotype and ploidy level indicating strongly impaired embryogenic potential of polyploid, aneuploid or other genetically altered cells.

Effects of tamoxifen on the levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17 beta-oestradiol (E2), total and free testosterone (T) and total and free dihydrotestosterone (DHT) in blood of patients with benign prostatic hyperplasia.

Treatment of 9 patients with benign prostatic hyperplasia with 20 mg tamoxifen daily for 6 weeks resulted in a significant increase of LH (211%), FSH (215%), E2 (231%), total T (157%), free T (148%) and total DHT (148%) levels in blood. The increase of plasma free DHT (152%) levels was not significant and PRL concentrations in serum were unchanged during treatment. Comparison of the increases between total T and free T, total T and total DHT as well as free T and free DHT failed to reveal any significant differences. These results imply (1) a marked anti-oestrogenic effect of tamoxifen at the level of hypothalamo-hypophysial axis (2) no effect at the hepatic oestrogen receptor sites indicated by unchanged SHBG-bound T and DHT in plasma and (3) no significant inhibitory effect of tamoxifen on 5 alpha-reductase activity concluded from the T/DHT ratio in peripheral circulation. In view of these findings tamoxifen appears to be unsuitable for therapy of benign prostatic hyperplasia.

Correlation between body and spleen weights in graft-versus-host reactions in the mouse.

The results reported here show the correlation between spleen (S) and body (B) weights in normal mice. This correlation is relevant to calculation of the spleen index in the graft-versus-host reaction (GVHR). By linear regression analysis a calibration curve B/S = f(B) could be calculated. This calibration curve provides a more reliable estimate of the strength of the GVHR since it compensated for the biological variance of the control values. This method of calculation further offers the possibility of pooling litters of different size and age (0-4 days postpartum) without loss of information due to additional variables.

Comparison of four mathematical models for the calculation of radioimmunoassay data of LH, FSH, and GH.

Weighted linear logit-log regression, point-to-point logit-log interpolation, smoothing spline approximation and the four-parameter logistic function calculated by non-linear regression have been compared. The data for comparison have been obtained from two different pool-sera for each of the LH-, FSH- and GH-RIA and from the basal serum LH values of two populations of children. The Wilcoxon matched pairs signed rank test was used for comparison: For GH there is no significant difference between all methods, for FSH the weighted linear logit-log regression and spline approximation appeared to be equivalent, but for LH no unequivocal assertion can be made. There is no significant difference between the mathematical models for determination of hormone concentration within one assay-run of a population as exemplified for LH. In addition, pool-sera data were subjected to an analysis of variance and the comparison of the results revealed that the different models did not lead to different statements about assay performance. The point-to-point logit-log interpolation is proposed as most simple curvilinear approximation for assays which cannot be linearized by logit-log transformation.

A simple strategy convenient for processing of RIA data and quality control in the laboratory on a desk-top-calculator.

The experience with a computer strategy of mathematically simple models for the description of standard curves and continuous quality control calculations with outlier diagnostics for the processing of RIA data in laboratory is discussed. To get over the difficulties associated with the approximation of the nonlinear shape of standard curves, the combination of weighted iterative linear logit-log regression and point-to point logit-log interpolation is proposed. Monitoring of assay performance is based on three large pool sera determined in triplicates. The control data are checked by statistical tests for the rejection of single outlying observations, followed by calculation of objective criteria on within- and between-assay precision by means of analysis of variance for a one-way classification on the basis of which actual triplicates and whole assays can be assessed. Combined with quality control chart technique and the construction of a rough three-point precision profile the empirical knowledge of an experienced assayist should be included in the RIA interpretation as can be easily organized by way of a dialogue-program on a desk-top-calculator.

Further studies on the hypothalamic desensitization to estrogen in immature female rats: evidence for a possible role in the control of puberty.

Immature and puberal female rats were ovariectomized and implanted with estradiol benzoate and cholesterol at the ratios of 1:120 or 1:240 into the hypothalamic ventromedial-arcuate region at 26 or 32 days of age, or on the day of the first vaginal estrus. Evaluation of the serum LH and FSH concentrations on the 2nd day after implantation revealed that the gonadotropin-inhibiting effect of the locally administered estrogen decreased between days 26 and 32 and showed a further distinct decline at the time of puberty. In a second experiment, uterine weight and serum LH and FSH levels were monitored in untreated immature female rats at daily intervals from 25 to 36 days of age. Relatively high values for both gonadotropins were recorded between days 25 and 28. Accelerated uterine growth around day 30 indicating increasing estrogen secretion was associated with a sudden decrease of LH and FSH concentration in the blood. After that, LH and, to a less degree FSH levels began to rise in spite of further weight gain of the uterus. The results suggest that the hypothalamic sensitivity to the gonadotropin-inhibiting effect of estrogen declines during the last week before the onset of puberty. Together with other findings they furthermore indicate that this desensitization process may be involved in the neurohormonal control of puberty in female rats.

Prenatal stress as possible aetiogenetic factor of homosexuality in human males.

Out of 865 homosexual males who were registered by venerologists in 6 districts of the GDR highly significantly more homosexuals were born during the stressful war and early postwar period of the Second World War, i.e. between 1941 and 1947 (with a maximum of relative frequency in 1944-1945), than in the years before or after this critical period. This finding suggests that stressful prenatal (or perinatal) events may represent an aetiogenetic factor for homosexuality in human males.

PAS-positive reaction of phenolic inclusions in plant cell vacuoles.

The experimental data presented show that positive reaction of phenolic inclusions in the PAS test may be caused by the presence of phenolic glycosides and/or certain non-glycosidic phenols, namely flavan-3,4-diols. These both possibilities and their respective importance under conditions of conventional histological procedures are discussed. The findings emphasize the need for extreme care in interpreting the results of the PAS reaction applied to plant material.

[Theoretical studies on the influence of binding constants of hemoglobin for ATP and 2,3-diphosphoglycerate on erythrocyte glycolysis]. / Theoretische Untersuchung über den Einfluss der Bindungskonstanten von Hämoglobin für ATP und 2,3-Diphosphoglyzerat auf die Erythrozytenglykolyse.

In the red blood cell exist a binding equilibrium of ATP and 2,3-DPG with hemoglobin. For the metabolism only the free active levels of organic phosphates are relevant. The binding constants of hemoglobin increase with decreasing temperature and pH. Using a stoichometric model of glycolysis, the change of free concentrations by altered binding constants and its import on the energy metabolism of the erythrocyte was theoretically studied. The results are: 1. Total ATP-content (bound plus free ATP) does not depend on the binding properties of hemoglobin. 2. Total 2,3-DPG-content is changed by altered binding constants of hemoglobin. The direction of change depends on the ratio energy-consumption/substrate-uptake. 3. In the case of strong binding of organic phosphates to hemoglobin the experimentally measurable total ATP-content does not reflect the free ATP-concentration in the cell water. As a result of binding, free ATP may be low even if total ATP is unchanged. 4. The free concentration of 2,3-DPG always parallels the total content.

[Importance of binding of 2,3-diphosphoglycerate and ATP to hemoglobin for erythrocyte glycolysis: activation by 2,3-diphosphoglycerate of hexokinase at intracellular conditions]. / Bedeutung der Bindung von 2,3-Diphosphoglyzerat und ATP an Hämoglobin für die Glykolyse in Erythrozyten: Aktivierung der Hexokinase durch 2,3-Diphosphoglyzerat unter intrazellulären Bedingungen.

In a theoretical study the influence of hemoglobin and Mg-ions as binding partners of red cell 2,3-diphosphoglycerate and ATP was investigated. Free hemoglobin may be an efficient competitor of Mg2+ for the ligand ATP. At conditions which favour hemoglobin as binding partner (i.e. desoxygenation, low medium pH and incubation temperature, as in blood preservation) up to 95% of the whole cellular ATP (ca. 2mM in cell water) may be bound to hemoglobin (ca. 7 mM). This binding is largely prevented in the presence of physiological amounts of diphosphoglycerate (ca. 7 mM) which is in excess and has a higher binding affinity to hemoglobin. Therefore, diphosphoglycerate keeps ATP (MgATP) in cell water solution at conditions in which Hb would trop it in the presence of Mg2+ (ca. 3mM). It can be calculated that, by lack of free MgATP, the activity of hexokinase within the cell drops by a factor of greater than 10 when diphosphoglycerate is metabolized. This indirect activation by diphosphoglycerate of hexokinase is operative at free concentrations of DPG far below those which exert the well known excess inhibitory effect on hexokinase and phosphofructokinase. In a model study, the activation by diphosphoglycerate of the initial two-kinase stage was introduced into a simplified kinetic model of glycolysis. A pronounced hysteresis loop of the stationary concentrations of ATP and diphosphoglycerate was produced indicating the existence of several stationary states, one with high ATP and high diphosphoglycerate, the other one with low values. It is demonstrated that diphosphoglycerate, being a protector of glycolysis at physiological concentrations, triggers an autocatalytic breakdown of the energy state when permitted to drop to low values.

[Effect of rapid changes of the oxygenation state and other external parameters on the long-term behavior of the energy metabolism in the erythrocyte]. / Einfluss schneller Bewegungen des Oxygenierungszustandes und anderer äusserer Parameter auf das Langzeitverhalten des Energiestoffwechsels der roten Blutzelle.

The red blood cell when transported through the circulatory system is exposed to a steady (approximately periodical) change of environmental conditions causing a permanent fluctuation of its important metabolic parameters. In a simple theoretical model it is demonstrated that a rapid oscillation of such parameters may stabilize a metabolic state which will collapse when this oscillation breaks off. The hypothesis is advanced that parameter oscillations caused by the physiological function of the red blood cell may be of importance for the maintenance of its energy metabolism and that the break-off of these oscillations may be a potential cause for the metabolic collapse, e.g. in stored blood.