HIV-1感染引起组蛋白乙酰化和增加p21WAF1表达

目的：DNA甲基化和组蛋白乙酰化是基因表达调控的主要形式。人类免疫缺陷病毒（HIV-1）可引起T淋巴细胞DNA甲基化酶上调。本文旨在明确HIV-1对细胞周期依赖刺激酶抑制剂p21^WAF1表达的影响。方法：建立HIV-1感染的Hut78细胞系；以RT-PCR和Westem blotting 分析p21^WAF1表达情况；以亚硫酸氢钠修饰DNA和基因测序，研究p21^WAF1基因启动子甲基化，以Western blot-ting 和染色体免疫测定探究总组蛋白和与p21^WAF1基因启动子相关的组蛋白乙酰化水平。并以GST pull-down和免疫沉淀分析HIV-1导致乙酰化及乙酰化引起p21^WAF1过表达的可能机理。结果：HIV-1感染后，其反式激活蛋白Tat与辅助转录因子P/CAF、hGCN5结合，共同刺激组蛋白H3乙酰化。尽管p21^WAF1启动子部分区域有甲基化发生，但p21^WAF1表达仍上调。这可能与E2A对p21^WAF1的作用有关。结论：HIV-1感染可引起T淋巴细胞p21^WAF1基因的甲基化和乙酰化紊乱，导致p21^WAF1表达增强。     

The effects of competition and motor reprogramming on visuomotor selection in unilateral neglect

Patients with unilateral neglect following right hemisphere damage may have difficulty in moving towards contralesional targets. To test the hypothesis that this impairment arises from competing motor programs triggered by irrelevant ipsilesional stimuli, we examined 16 right hemisphere patients, eight with left visual neglect and eight without, in addition to eight healthy control subjects. In experiment 1 subjects performed sequences of movements using their right hand to targets on the contralesional or ipsilesional side of the responding limb. The locations of successive targets in each sequence were either predictable or unpredictable. In separate blocks of trials, targets appeared either alone or with a simultaneous distractor located at the immediately preceding target location. Neglect patients were significantly slower to execute movements to contralesional targets, but only for unpredictable movements and in the presence of a concurrent ipsilesional distractor. In contrast, healthy controls and right hemisphere patients without neglect showed no directional asymmetries of movement execution. In experiment 2 subjects were required to interrupt a predictable, reciprocating sequence of leftward and rightward movements in order to move to an occasional, unpredictable target that occurred either in the direction opposite to that expected, or in the same direction but twice the extent. Neglect patients were significantly slower in reprogramming the direction and extent of movements towards contralesional versus ipsilesional targets, and they also made significantly more errors when executing such movements. Right hemisphere patients without neglect showed a similar bias in reprogramming direction (but not extent) for contralesional targets, whereas healthy controls showed no directional asymmetry in either condition. On the basis of these findings we propose that neglect involves a competitive bias in favour of motor programs for actions directed towards ipsilesional versus contralesional events. We suggest that programming errors and increased latencies for contralesional movements arise because the damaged right hemisphere can no longer effectively inhibit the release of inappropriate motor programs towards ipsilesional events. Received: 1 October 1996 / Accepted: 21 October 1997     

Intracellular mechanism of quinidine action on muscle contraction

Summary The mechanism of quinidine action on rabbit cardiac and skeletal muscle was examined with functionally skinned muscle-fiber preparations. By using these preparations we could correlate measurements of muscle tension with the effect of quinidine on the Ca²⁺ activation of the contractile proteins and on the Ca²⁺ uptake and release from the sarcoplasmic reticulum (SR). Effect of quinidine on the contractile proteins. Quinidine concentrations above 0.5 mmol/l increased the maximal Ca²⁺-activated tension development 12% for papillary muscle and 5% for soleus (slow-twitch). Adductor magnus (fast-twitch) showed no significant change. Quinidine (0.1–1.0 mmol/l) also increased the submaximal Ca²⁺-activated tension development for the three muscle types (papillary muscle=soleus>adductor magnus) and shifted the [Ca²⁺]-tension curves to the left in a dose-dependent fashion. Effects of quinidine on the Ca ²⁺ uptake and release from the SR. Sarcoplasmic reticulum of skinned fibers was loaded with Ca²⁺ (uptake phase), then Ca²⁺ was released by 25 mmol/l caffeine (release phase) giving a tension transient. The area under the tension transient was used to estimate the amount of Ca²⁺ released. Quinidine (>0.5 mmol/l) decreased the Ca²⁺ uptake (soleus>adductor magnus>papillary muscle) and increased the Ca²⁺ release [papillary muscle=soleus adductor magnus (only at 1.5 mmol/l, the highest concentration tested)] from the SR of all three muscles in a dose-dependent manner. Quinidine at low concentration (0.1 and 0.5 mmol/l) increased the caffeine-induced tension transient of papillary muscle and higher quinidine concentrations (1.0 and 1.5 mmol/l) decreased the caffeine-induced tension transient of soleus and adductor magnus during both the uptake and release phases. The decreased Ca²⁺ uptake of papillary muscle in 1.5 mmol/l quinidine was antagonized by increasing the free Mg²⁺ from 0.032 to 0.32 mmol/l.In summary, quinidine has similar mechanisms of action in all three muscles: increased Ca²⁺ activation of the contractile proteins, decreased Ca²⁺ uptake and increased Ca²⁺ release from the SR in functionally skinned muscle fibers. We conclude that quinidine-induced decreases in Ca²⁺ uptake by the SR could be responsible for quinidine-induced myocardial depression and that quinidine-induced increases in Ca²⁺ activation of the contractile proteins and Ca²⁺ release from the SR could be responsible for the increases in skeletal muscle contraction caused by quinidine.     

Effects of a Rice Bran Dietary Intervention on the Composition of the Intestinal Microbiota of Adults with a High Risk of Colorectal Cancer: A Pilot Randomised-Controlled Trial

Rice bran exhibits chemopreventive properties that may help to prevent colorectal cancer (CRC), and a short-term rice bran dietary intervention may promote intestinal health via modification of the intestinal microbiota. We conducted a pilot, double-blind, randomised placebo-controlled trial to assess the feasibility of implementing a long-term (24-week) rice bran dietary intervention in Chinese subjects with a high risk of CRC, and to examine its effects on the composition of their intestinal microbiota. Forty subjects were randomised into the intervention group (n = 19) or the control group (n = 20). The intervention participants consumed 30 g of rice bran over 24-h intervals for 24 weeks, whilst the control participants consumed 30 g of rice powder on the same schedule. High rates of retention (97.5%) and compliance (≥91.3%) were observed. No adverse effects were reported. The intervention significantly enhanced the intestinal abundance of Firmicutes and Lactobacillus, and tended to increase the Firmicutes/Bacteroidetes ratio and the intestinal abundance of Prevotella_9 and the health-promoting Lactobacillales and Bifidobacteria, but had no effect on bacterial diversity. Overall, a 24-week rice bran dietary intervention was feasible, and may increase intestinal health by inducing health-promoting modification of the intestinal microbiota. Further larger-scale studies involving a longer intervention duration and multiple follow-up outcome assessments are recommended.     

A National Survey of Breast Surgeons and Radiation Oncologists on Contemporary Axillary Management in Mastectomy Patients

Annals of Surgical Oncology - Management of axillary lymph nodes in breast cancer has undergone significant change over the past decade through landmark clinical trials. This study aimed to assess...