Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism.

In a blinded study, 159 subjects composed of nonalcoholics (N = 43), less severe alcoholics (N = 44), severe alcoholics (N = 52) and young children of alcoholics (CoAs, N = 20) were studied for their allelic association with the D2 dopamine receptor (D2DR) gene utilizing peripheral lymphocytes as the DNA source. The combined alcoholic group compared to the nonalcoholic group showed a significantly greater association with the A1 allele of the D2DR gene. Furthermore, an even more robust association was found when severe alcoholics were compared to nonalcoholics. CoAs also showed a significantly greater association with the A1 allele than nonalcoholics but not when compared to alcoholics. Analysis of risk of alcoholism severity suggests that it comprises of two independent components: family history of alcoholism and presence of the A1 allele. Genotype and allelic frequency of the D2DR gene were also analyzed with respect to race. A higher percentage of blacks compared to whites had the A1/A1 genotype, and A1 allelic frequency in the total sample of blacks was significantly greater than in the total sample of whites. Moreover, frequency of the A1 allele was significantly greater in severe alcoholics compared to nonalcoholics in both whites and blacks. However, due to the small sample size of blacks, these racial differences need to be further studied. This study, of the largest sample of alcoholics to date, strongly affirms association of severe alcoholism with the A1 allele of the D2DR gene.     

A factor analysis of the rat''s corpus callosum

Previous work from our laboratory (Berrebi et al., Brain Research, 438 (1988) 216-224) demonstrated region-specific sexual dimorphisms in the size of the rat's corpus callosum, which are modifiable by extra stimulation in early life. These differences are assumed to reflect regional corticocortical fibers of passage which are altered differentially by gender and our experimental manipulations. In this paper, we report our findings when the original data are reanalyzed using a newly developed computer program. This program not only reproduced, with very high accuracy, the original means, but also permitted us to examine computer generated callosal width scores via a factor analysis procedure. Such a procedure yields useful information concerning the clustering of callosal fibers and thus contributes significantly to our hypothesis that discrete cortical regions are selectively sensitive to experimental variables. Factor analyses of the callosal variables and brain weight of 155 rats found 7 width factors, and an eighth factor which contained the variables of brain weight, callosal length, and callosal perimeter. Callosal area did not load significantly on any of these factors. The percentile locations of the width factors, starting at the anterior (genu) end were: widths 1-5, 6-17, 24-38, 46-57, 62-72, 79-95 and 96-99. Use of these factor scores in analyses of variance revealed that the male callosum is wider than the female's, with the differences most pronounced in the genu and the most posterior portion of the splenium. Both age and early handling experience influenced the callosal width factors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Living after cancer: challenges in being a survivor.

Concerns about survivorship and the needs of cancer survivors are occurring with increasing frequency (Ferral, Virani, Smith & Juarez, 2003; Curtiss & Haylock, 2006). Advances in the diagnosis and treatment of cancer have resulted in an ever-growing cadre of individuals who are survivors of the disease. In United States alone, there are more than 10 million cancer survivors (ACS, 2005). In Canada, there are almost 800,000-a comparable number given the country's population (NCIC, 2006). Approximately 60% of adults who are diagnosed with the disease and 78% of the children are alive at five years (ACS, 2005). Given the expectation that the number of people diagnosed with cancer will double in the next 40 years, we can expect the number of survivors will also continue to increase. Living after a diagnosis of cancer and its subsequent treatment is not without its challenges. We are only now beginning to recognize some of the concerns and issues survivors face and what a vulnerable population these individuals constitute. The growing number of individuals in our midst has allowed us to start learning about the challenges survivors can face on a daily basis. Their voices are being heard as advocacy group representatives speak out about their needs and the gaps in cancer service delivery. We are beginning to identify the spectrum of late complications survivors may experience with the potential to compromise quality of life. We are also beginning to recognize that the late and long-term effects are more prevalent, serious, and persistent than was originally expected.     

The dendritic morphology of pyramidal neurons in the rat hippocampal CA3 area. II. Effects of gender and the environment

Sex differences in the dendritic structure of hippocampal CA3 pyramidal neurons were studied in Golgi-stained tissue from hooded rats that had been raised in either a relatively complex or an isolated environment from weaning for one month. Pyramidal neurons were sampled from both the short-shaft and long-shaft neuron categories as described by Fitch et al. The pattern of sex differences varies in different parts of the apical dendritic tree. In the apical tree proximal to the soma, females had more dendritic material than males. This pattern was attributable to the sex differences in the short-shaft neurons of rats from the more complex environment. The direction of sex differences was reversed in the distal apical dendritic tree where males had more dendritic material than females. As in the proximal dendritic tree, this pattern of sex differences stemmed from the short-shaft neurons of rats from the more complex environment. There were no sex differences in the basilar dendritic tree. Thus sex differences in the pyramidal neurons of hippocampal area CA3 vary with the portion of the dendritic tree examined, the type of pyramidal neuron, and the rearing environment of the animal.     

Chloroquine-Resistant Plasmodium falciparum: Effect of Substrate on Chloroquine and Amodiaquin Accumulation

Glucose stimulates the high-affinity processes of chloroquine and amodiaquin accumulation in owl monkey erythrocytes infected with a chloroquine-susceptible strain of Plasmodium falciparum. Although these erythrocytes have greater ability to accumulate amodiaquin than chloroquine, glucose has relatively less effect on amodiaquin accumulation than on chloroquine accumulation. In contrast to these findings with chloroquine-susceptible P. falciparum, glucose stimulates amodiaquin but not chloroquine accumulation in erythrocytes infected with chloroquine-resistant P. falciparum. This lack of function of a substrate-dependent component of chloroquine accumulation distinguishes chloroquine-resistant from chloroquine-susceptible P. falciparum.     

Hemolysis of mouse erythrocytes by ferriprotoporphyrin IX and chloroquine. Chemotherapeutic implications.

Incubation of a 0.5% suspension of washed normal mouse erythrocytes with ferriprotoporphyrin IX (FP) for 2.5 h at 37 degrees C and pH 7.4 results in sufficient membrane damage to produce hemolysis. A sigmoidal dose-response curve is followed with 50% hemolysis being produced by 4 microM FP. Complete hemolysis is produced by 6 microM FP. The hemolytic process has at least two phases: a lag phase of approximately 45 min, during which little hemolysis occurs, and a phase characterized by rapid hemolysis. Chloroquine, which binds tightly to FP, enhances the effect of FP by eliminating the lag phase. Under the conditions of these experiments, maximum enhancement is observed with chloroquine concentrations in the range of 5-25 microM. Since FP is produced when malaria parasites digest hemoglobin, it may mediate a chemotherapeutic effect of chloroquine by forming a complex with the drug that could enhance the toxicity of FP for biological membranes, including those of the parasite.     

Regulation of heme polymerizing activity and the antimalarial action of chloroquine.

Mice infected with Plasmodium berghei served as donors of erythrocytes with a high level of parasitemia for the study of ferriprotoporphyrin IX (FP) polymerization. Six hours after treatment of these mice with 3 micromol of chloroquine per 25 g of body weight, there were significant losses of heme polymerase I (HPA I). For chloroquine-susceptible (CS) P. berghei, the rate of FP polymerization decreased from 541 +/- 42 (mean +/- standard deviation; n = 12) to 51 +/- 19 (n = 8) nmol of FP polymerized per h per ml of packed erythrocytes (normalized to represent 1,000 parasites per 1,000 erythrocytes). For chloroquine-resistant (CR) P. berghei, the rate decreased from 284 +/- 19 (n = 16) to 124 +/- 11 (n = 6) nmol per h per ml. The chloroquine-induced loss of HPA I was accompanied by the accumulation of unpolymerized FP in CS P. berghei but not in CR P. berghei, which is consistent with the hypothesis that FP mediates the antimalarial action of chloroquine. Quinine treatment partially reversed the effects of chloroquine in CS P. berghei but not in CR P. berghei. Cycloheximide treatment antagonized the effects of chloroquine in both lines of parasites. To explain these findings, we propose that chloroquine, quinine, and cycloheximide perturb a regulatory process for HPA I. Furthermore, we propose that when chloroquine engages its target in the regulatory process, it initiates a chain of events which culminates in increased production, accessibility, or reactivity of a regulator (inactivator) of HPA I.