Short term increase in risk of breast cancer after full term pregnancy.

To determine whether there is a short term increase in the risk of breast cancer after a full term birth data from two hospital based, case-control studies in Italy were pooled. Analysis was restricted to women aged under 50 with two or more children (573 women with cancer and 570 controls). A relative risk for breast cancer of 2.66 was seen in women who had given birth during the three years preceding the interview compared with women whose last birth had occurred 10 or more years before, after adjustment for age, age at first birth, and parity. The relative risk slowly decreased for women who had last given birth three to 10 years before. Multivariate analyses confirmed the protective effect of an early age at first birth and the age dependent effect of parity on the risk of breast cancer--that is, a direct relation below age 40 and an inverse one in older women. These data provide epidemiological evidence that a full term birth is followed by a transient increase in the risk of breast cancer, which for some time contrasts with and overcomes the long term protection of pregnancy at an early age. They therefore confirm predictions from animal studies and theoretical models that pregnancy prevents the early stages of breast carcinogenesis but promotes the late stages of the process.     

Internucleosomal DNA fragmentation is not obligatory for castration induced rat ventral prostate cell apoptosis in vivo

Castrated male rats were treated with the reversible S1-phase cell cycle blocking drug, mimosine, and the effects of this drug on prostate cell apoptosis was characterized. At a single dose of mimosine (25 mg/kg/day), we found that the internucleosomal DNA fragmentation associated with apoptosis was partially suppressed in the rat ventral prostate at all early time points (24, 48 and 72 h) analyzed post-castration. This suppression was dose-dependent, and treatment with mimosine up to 150 mg/kg/day was sufficient to reduce the internucleosomal DNA fragmentation in the prostate by 90% at 72 h post-castration. Intriguingly, this drug did not suppress the induction of mRNAs for several apoptosis-associated gene products in the ventral prostate gland (bcl-2, p53, TGF-beta and SGP-2/clusterin). Moreover, this treatment did not suppress the histological appearance of apoptotic bodies in the ventral prostate detectable by fast green staining of thin sections of tissue. The apoptotic bodies present in mimosine-treated regressing ventral prostate tissues, however, were refractory to labeling by the in situ gap labeling method, further demonstrating lack of nuclear DNA fragmentation in the condensed nuclei of apoptotic cells. In summary, the cell cycle-blocking drug mimosine does not appear to affect the rate of apoptosis in the regressing rat ventral prostate gland. However, this drug was capable of suppressing the nuclear DNA fragmentation associated with androgen-regulated prostate cell apoptosis. These results support the concept that nuclear DNA fragmentation is not obligatory for apoptosis. Additionally, they imply that cell cycle movement from the G1/S-phase boundary might be important for the terminal DNA degradation associated with androgen-regulated prostate cell apoptosis.     

DROSOPHILA S2 cell culture in a WAVE Bioreactor: potential for scaling up the production of the recombinant rabies virus glycoprotein

Applied Microbiology and Biotechnology - The transmembrane rabies virus glycoprotein (RVGP) is the main antigen of vaccine formulations used around the world to prevent rabies, the most lethal...     

Different associations of white matter lesions with depression and cognition

ABSTRACT: BACKGROUND: To test the hypothesis that white matter lesions (WML) are primarily associated with regional frontal cortical volumes, and to determine the mediating effects of these regional frontal cortices on the associations of WML with depressive symptoms and cognitive dysfunction. METHODS: Structural brains MRIs were performed on 161 participants: cognitively normal, cognitive impaired but not demented, and demented participants. Lobar WML volumes, regional frontal cortical volumes, depressive symptom severity, and cognitive abilities were measured. Multiple linear regression analyses were used to identify WML volume effects on frontal cortical volume. Structural equation modeling was used to determine the MRI-depression and the MRI-cognition path relationships. RESULTS: WML predicted frontal cortical volume, particularly in medial orbirtofrontal cortex, irrespective of age, gender, education, and group status. WML directly predicted depressive score, and this relationship was not mediated by regional frontal cortices. In contrast, the association between WML and cognitive function was indirect and mediated by regional frontal cortices. CONCLUSIONS: These findings suggest that the neurobiological mechanisms underpinning depressive symptoms and cognitive dysfunction in older adults may differ.     

Spatial Distribution of Genetic Variation in a Natural Beech Stand (Fagus sylvaticaL.) Based on Microsatellite Markers

The spatial distribution of alleles is described in a naturally regenerated, isolated pure beech (Fagus sylvaticaL.) stand consisting of 99 adult trees. After testing nine microsatellite loci originally developed for F. crenata, each tree was genotyped at four well-scorable microsatellite loci. Specific primers were developed for one locus of F. sylvaticaL. For the characterization of spatial genetic structures, two different statistics were used. One method is based on the mean genetic distance between trees in different spatial distance classes, and the other one is Moran's index I. The results show the same tendency of a strong family structure in the distance classes up to 30m in comparison with that expected for a spatially non-systematic distribution of genotypes. In general, microsatellites are more useful to detect spatial genetic structures than allozymes. Spatial genetic structures are influenced by unpredictable factors such as wind direction at anthesis and can therefore vary from year to year. We recommend that seed collections should cover large areas in order to prevent a preponderance of few families and a reduction of the adaptive potential of the next generation.     

Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects

The hypotheses that postexercise replenishment of intramyocellular lipids (IMCL) is enhanced by endurance training and that it depends on fat intake were tested. Trained and untrained subjects exercised on a treadmill for 2 h at 50% peak oxygen consumption, reducing IMCL by 26-22%. During recovery, they were fed 55% (high fat) or 15% (low fat) lipid energy diets. Muscle substrate stores were estimated by (1)H (IMCL)- and (13)C (glycogen)-magnetic resonance spectroscopy in tibialis anterior muscle before and after exercise. Resting IMCL content was 71% higher in trained than untrained subjects and correlated significantly with glycogen content. Both correlated positively with indexes of insulin sensitivity. After 30 h on the high-fat diet, IMCL concentration was 30-45% higher than preexercise, whereas it remained 5-17% lower on the low-fat diet. Training status had no significant influence on IMCL replenishment. Glycogen was restored within a day with both diets. We conclude that fat intake postexercise strongly promotes IMCL repletion independently of training status. Furthermore, replenishment of IMCL can be completed within a day when fat intake is sufficient.     

Differences in hepatic and metabolic changes after acute and chronic alcohol consumption.

Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system. Since the major fraction of ethanol metabolism proceeds via alcohol dehydrogenase and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate microsomal ethanol oxidizing system pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Severe hepatic lesions (alcoholic hepatitis and cirrhosis) develop after prolonged ethanol consumption in baboons. These injurious alterations are not prevented by nutritionally adequate diets and can therefore be ascribed to ethanol rather than to dietary inadequacy.