Conduct disorder with and without mania in a referred sample of ADHD children

OBJECTIVE: To test the hypothesis that dysphoric and non-dysphoric types of CD could be distinguished from one another in their patterns of familiality, adversity, and comorbidity. METHODS: We examined 140 ADHD and 120 normal controls at baseline and 4 years later using assessments from multiple domains. We compared ADHD subgroups with and without conduct (CD) and bipolar (BPD) disorders on psychiatric outcomes at a 4-year follow-up, familial psychopathology and psychosocial functioning. RESULTS: We found that ADHD children with both disorders had higher familial and personal risk for mood disorders than those with CD only, who had a higher personal risk for antisocial personality disorder. Among ADHD probands, having both CD and BPD was associated with poorer functioning and an increased risk for psychiatric hospitalization. DISCUSSION: Although preliminary, our findings suggest that the distinction between dysphoric and non-dysphoric CD may be clinically meaningful. If confirmed, our findings could have important diagnostic and therapeutic implications for the management of antisocial youth.     

Distinct roles of the interleukin-7 receptor alpha chain in fetal and adult thymocyte development revealed by analysis of interleukin-7 receptor alpha-deficient mice

Mouse mutants lacking expression of the IL-7 receptor (IL-7R) alpha chain are defective in thymopoiesis. The adult thymus has multiple defects, including reduced cell numbers and proportions of the more mature thymocyte subsets, a complete absence of CD25+ cells and a reduced level of RAG1 and RAG2 expression. We show here that, in contrast to the profound developmental arrest observed in the adult thymus, fetal thymocytes from IL-7Ralpha-/- mice have normal proportions of all of the major thymocyte subpopulations, including CD25+ thymocytes and the most mature single-positive subsets. Moreover, normal levels of RAG1 and RAG2 were observed. Total thymocyte numbers, however, remained reduced. These data suggest that the IL-7Ralpha chain is a key regulator of both survival and proliferation during thymocyte development but that it is not essential for the production of T cells during fetal thymopoiesis.     

Functional stereotaxy with magnetic resonance tomographic guidance

The paper summarizes experience with stereotactic operations by magnetic resonance imaging data by using a Russian OREOL stereotactic manipulator. It describes methods of preoperative preparation of patients by employing diagnostic magnetic resonance tomographs. A number of points of the procedure for identification and localization of deep target structures from magnetic resonance images in parkinsonism, temporal epilepsy and some mental disorders.     

Mechanism of action of human P-glycoprotein ATPase activity. Photochemical cleavage during a catalytic transition state using orthovanadate reveals cross-talk between the two ATP sites

Human P-glycoprotein (P-gp), an ATP-dependent efflux pump responsible for cross-resistance of human cancers to a variety of lipophilic compounds, is composed of two homologous halves, each containing six transmembrane domains and an ATP-binding/utilization domain. To determine whether each site can hydrolyze ATP simultaneously, we used an orthovanadate (Vi)-induced ADP-trapping technique (P-gp.MgADP.Vi). In analogy with other ATPases, a photochemical peptide bond cleavage reaction occurs within the Walker A nucleotide binding domain consensus sequence (GX4GK(T/S)) when the molecule is trapped with Vi in an inhibited catalytic transition state (P-gp.MgADP.Vi) and incubated in the presence of ultraviolet light. Upon reconstitution into proteoliposomes, histidine-tagged purified P-gp from baculovirus-infected insect cells had drug-stimulated ATPase activity. Reconstituted P-gp was incubated with either ATP or 8-azido-ATP in the presence or absence of Vi under ultraviolet (365 nm) light on ice for 60 min. The resultant products were separated by SDS-polyacrylamide gel electrophoresis and subjected to immunoblotting with seven different human P-gp-specific antibodies covering the entire length of the molecule. Little to no degradation of P-gp was observed in the absence of Vi. In the presence of Vi, products of approximately 28, 47, 94, and 110 kDa were obtained, consistent with predicted molecular weights from cleavage at either of the ATP sites but not both sites. An additional Vi-dependent cleavage site was detected at or near the trypsin site in the linker region of P-gp. These results suggest that both the amino- and carboxyl-terminal ATP sites can hydrolyze ATP. However, there is no evidence that ATP can be hydrolyzed simultaneously by both sites.     

The relationship between lipid peroxidation and life span in Drosophila melanogaster

Using Drosophila lines pre-selected for adaptive characters, studies have been made on the relationship between the intensity of lipid peroxidation and life span in flies of different genotype, age and physiological condition. It was shown that the intensity of lipid peroxidation depends mainly on different factors (sex, age, virginity) in different lines. No expected negative correlation was found between the level of lipid peroxidation and life span in hybrids between two inbred lines. The intensity of lipid peroxidation was inherited like a dominant character, the dynamics of aging--like a codominant one in females and superdominant in males. Both the level of lipid peroxidation and life span appeared to be sex-dependent characters.     

Cytotoxicity of weak electrolytes after the adaptation of cells to low pH: role of the transmembrane pH gradient

Theory suggests that the transmembrane pH gradient may be a major determinant of the distribution of lipophilic weak electrolytes across the cell membrane. The present study evaluates the extent to which this factor contributes to pH-dependent changes in the cytotoxicity of two such chemotherapeutic drugs: chlorambucil and mitoxantrone. Experiments were performed with two cell types of the same origin but exhibiting different pH gradients at the same extracellular pH (pHe): CHO cells cultured under normal physiological conditions (pH 7.4) and acid-adapted cells obtained by culturing under low pH conditions (6.8). Over the pHe range examined (6.0-7.6), the difference between intracellular pH (pHi) and pHe increased with decreasing pHe. Acid-adapted cells were more resistant to acute changes in pHi than normal cells, resulting in substantially larger gradients in these cells. Drug cell survival curves were performed at pHe values of 6.4, 6.8 and 7.4. The cytotoxicity of chlorambucil, a weak acid, increased with decreasing pHe, and low pH-adapted cells were more sensitive than normal cells at the same pHe. In contrast, for the weak base, mitoxantrone, cytotoxicity increased with pHe and was more pronounced in normal cells. As predicted by the theory, the cytotoxicity of both drugs changed exponentially as a function of the pH gradient, regardless of cell type. For mitoxantrone, the rate of such change in cytotoxicity with the gradient was approximately two times greater than for chlorambucil. This difference is probably due to the presence of two equally ionizable crucial groups on mitoxantrone vs one group on chlorambucil. It is concluded that the cellular pH gradient plays a major role in the pH-dependent modulation of cytotoxicity in these weak electrolytes. The data obtained also suggest that a pronounced differential cytotoxicity may be expected in vivo in tumour vs normal tissue. In comparison with normal cells at a pHe of 7.4 (a model of cells in normal tissues), acid-adapted cells at a pHe of 6.8 (a model of cells distal from supplying blood vessels in tumours) were more sensitive to chlorambucil, with a dose-modifying factor of approximately 6, and were more resistant to mitoxantrone by a factor of 14.     

Can parental longevity and self-rated life expectancy predict mortality among older persons? Results from an Australian cohort

This study examined the effects of parental longevity and self-rated life expectancy on mortality, building upon the established model of self-rated health predicting mortality. A community sample of Australians aged 70 and over was surveyed in 1992 and 1995. The associations of interest were examined separately by sex using weighted multiple logistic regression. Parental ages at death were not associated with mortality for either men or women. In multivariate models, self-rated life expectancy had an independent effect on men's mortality and did not reduce the effect of self-rated health on mortality. Our findings from Australia are consistent with results from many countries; the effect of self-rated health on mortality is stronger for men than for women. We also found that the effect of self-rated life expectancy on mortality is stronger for men than for women. The independent effects of self-rated health and self-rated life expectancy indicate a need for a more detailed search for explanatory mechanisms.