An analysis of two recent epidemiologic reports in the New England Journal of Medicine associating breast cancer in women with moderate alcohol consumption

Two cohort studies showed an association between moderate alcohol consumption and breast cancer, with an apparent relative risk of 1.50. Drinkers and nondrinkers already differed in important ways at the initiation of these two studies, precluding a causal interpretation of the associations found. Women in need of the relaxing effect of alcohol may indeed be the group at higher risk for breast cancer. Inasmuch as the studies did not inquire into other cancers, morbidities, mortalities, or total mortality, they leave open the possibility that, on balance, moderate alcohol consumption is beneficial.     

Fetal motility and chronic exposure to antiepileptic drugs.

The potential influence of antiepileptic drugs (AEDs) on fetal CNS function was studied with respect to motility patterns. Quantitative and qualitative aspects of spontaneous fetal activity were investigated for chronic AED-exposed fetuses and controls at three intervals during pregnancy: i.e. 20, 32 and 38 weeks. Movements were observed applying real-time ultrasound. Third trimester rest-activity cycles were determined according to the fetal behavioural state concept. Quantitative analysis revealed no marked differences in gross fetal motility between AED-exposed fetuses and controls. Both groups demonstrated the same developmental trend from midterm towards the third trimester. The number of trunk movements decreased, while their median duration increased. The incidence of fetal eye movements during C2F was lower for AED-exposed fetuses than for controls (significant for 38 weeks). In qualitative analysis, general movements of AED-exposed fetuses were more often labeled as suspect or abnormal than those of control fetuses (respectively, 8 out of 31 and 1 out of 20; P = 0.06). Future studies concerning chronic fetal AED-exposure and fetal CNS function should focus on qualitative rather than quantitative aspects of motility.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

大鼠胸腺降黑素受体的鉴定及生物学特性

应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位，该结合位点可以满足特异结合部位的基本条件：１．低结合容量；２．高亲和力；３．可饱和性；４．可逆性；５．对降黑素高度特异性。此外，该特异结合位点具昼夜节律；亚细胞分布的研究表明以细胞核含量最高，线粒体次之，并具有年龄依赖性降低，以出生时最高。     

The effects upon the activity of hand and forearm muscles of intracortical stimulation in the vicinity of corticomotor neurones in the conscious monkey

Summary Corticomotor (CM) neurones were identified in three conscious macaque monkeys by the presence of post-spike facilitation (PSF) in spike-triggered averages of e.m.g. recorded from intrinsic hand and forearm muscles during performance of a precision grip task. Post-spike effects were compared with those produced by single-pulse intracortical microstimulation (ICMS), with strengths of 4–20 A, delivered at the site of 47 CM cells. Most muscles facilitated by a CM cell were also facilitated by ICMS at the site of the cell. ICMS effects were stronger: at 10 A, the amplitude of ICMS-evoked facilitation was on average 2.8 times greater than PSF, and 6.9 times greater at 20 A. Onset latency of ICMS-evoked facilitation was consistently longer (by 1.7 and 1.3 ms at 10 and 20 A respectively) than PSF, and it is suggested that this results from the indirect, trans-synaptic excitation of CM cells by ICMS. Post-spike suppression was rarely seen (7/421 compared to 105/421 cases of PSF). In contrast, suppression and facilitation were equally common in response to ICMS. The synaptic mechanisms underlying these effects were explored in 5 anaesthetised macaque monkeys. ICMS facilitated a greater proportion of the tested muscles than did the CM cell recorded at the stimulus site. The results suggest the juxtaposition in the motor cortex of CM neurones with different muscle fields. The merits of STA and ICMS for exploring cortical organisation are discussed.     

Automated analysis of near-term antepartum fetal heart rate in relation to fetal behavioral states: the Sonicaid System 8000.

Fetal heart rate and fetal movements were recorded in 16 uncomplicated near-term pregnancies. The recordings were used to evaluate a system for automated fetal heart rate analysis (Sonicaid System 8000). Fetal rest-activity patterns were considered in the analysis. The mean duration of C2F periods "active sleep," 33 minutes) was significantly greater than that of C1F periods ("quiet sleep," 19 minutes) (p less than 0.001). The incidence of accelerations and decelerations and the overall fetal heart rate variations were greater during C2F than during C1F (p less than 0.001). In 11 of 16 C1F periods, the system classified the fetal heart rate variation as "questionable" or "abnormal." Episodes of high variation were identified in only 3 of 16 C1F periods, but they were found in all 18 C2F periods. Episodes of low variation were identified in 14 of the 16 C1F periods but were not found in any C2F periods. During C2F periods, the system's criteria of normality were met in all cases but one; they were not met during any of the C1F periods. Thus the diagnosis of fetal distress should not be based merely on the absence of accelerations, low fetal heart rate variation, or absence of episodes of high variation in recordings with a duration of less than 45 minutes.