破坏泛素依赖的蛋白水解通路对p53转录激活的抑制作用

目的 :研究功能性泛素化及蛋白酶体水解过程对p5 3转录激活的影响。方法 :通过瞬时转染报告基因法 ,测定内源、外源性p5 3或p5 3转录活性片断的转录能力 (荧光素酶活性 ) ;Western blot法测定细胞内p5 3及其靶蛋白p2 1waf1 的表达水平。结果 :抑制蛋白酶体水解过程 ,细胞内源、外源性p5 3及p5 3转录活性片断的转录能力均降低 ;泛素化途径缺失时 ,p5 3转录能力被显著抑制 ,虽然细胞内p5 3蛋白堆积 ,但其下游靶蛋白p2 1waf1 的表达却无增加。结论 :p5 3泛素蛋白酶体水解途径与其转录激活过程存在功能性联系     

Neurologic dysfunction in patients with rheumatoid arthritis of the cervical spine. Predictive value of clinical, radiographic and MR imaging parameters

The aim of this study was to evaluate if subjective symptoms, radiographic and especially MR parameters of cervical spine involvement, can predict neurologic dysfunction in patients with severe rheumatoid arthritis (RA). Sequential radiographs, MR imaging, and neurologic examination were performed yearly in 46 consecutive RA patients with symptoms indicative of cervical spine involvement. Radiographic parameters were erosions of the dens or intervertebral joints, disc-space narrowing, horizontal and vertical atlantoaxial subluxation, subluxations below C2, and the diameter of the spinal canal. The MR features evaluated were presence of dens and atlas erosion, brainstem compression, subarachnoid space encroachment, pannus around the dens, abnormal fat body caudal to the clivus, cervicomedullary angle, and distance of the dens to the line of McRae. Muscle weakness was associated with a tenfold increased risk of neurologic dysfunction. Radiographic parameters were not associated. On MR images atlas erosion and a decreased distance of the dens to the line of McRae showed a fivefold increased risk of neurologic dysfunction. Subarachnoid space encroachment was associated with a 12-fold increased risk. Rheumatoid arthritis patients with muscle weakness and subarachnoid space encroachment of the entire cervical spine have a highly increased risk of developing neurologic dysfunction. Received: 31 December 1999 Revised: 30 May 2000 Accepted: 5 June 2000     

Ketamine anesthesia with or without diazepam premedication for bone marrow punctures in children with acute lymphoblastic leukemia

Ketamine is a drug widely used for analgesia and sedation of children for diagnostic and therapeutic procedures. The authors investigated in a randomized controlled clinical trial if diazepam premedication would have a beneficial effect on side effects related to ketamine anesthesia for bone marrow punctures (BMPs) in children with acute lymphoblastic leukemia (ALL). Sixteen children 4 years or older at the time of BMP were eligible. The first 2 BMPs after complete remission was obtained were studied. BMPs were performed under ketamine anesthesia (1.0-1.5 mg/kg iv), as usual. Patients were randomized to receive 1 h before the first BMP blinded, either diazepam or placebo orally and before the second BMP the other way round. Blood pressure, heart rate, and oxygen saturation were monitored, and patients were observed for signs of anxiety, pain, and other side effects. The patients were interviewed after each BMP and asked for their preference 1 week after the second BMP. Ketamine anesthesia appeared as safe and effective after diazepam premedication as after placebo premedication. From the interviews and questionnaires, it was clear that half of the children preferred diazepam premedication because of less awful dreaming and more gradual falling asleep and waking up. Diazepam premedication may be useful for selected children with ALL receiving ketamine anesthesia for BMPs.     

The role of steroid hormones in protogynous sex change in the Blackeye goby, Coryphopterus nicholsii (Teleostei: Gobiidae)

To detect and describe correlations between steroid concentrations and sexual function in the protogynous Coryphopterus nicholsii, we examined whole-body concentrations of the gonadal steroids testosterone (T), 11-ketotestosterone (11-KT), and 17beta-estradiol (17beta-E2). Our results show that T, 11-KT, and 17beta-E2 are naturally occurring steroids in both female and male C. nicholsii. Further, mean whole-body concentrations of T and 11-KT in males were approximately twice those in females, whereas mean whole-body concentration of 17beta-E2 in females was almost twice that in males. Second, we tested hypotheses on the causation of sex change arising from these correlations between steroid concentrations and sexual function. We examined the effects of administration of 11-KT, 11-KA, 17alpha-methyltestosterone, and an aromatase inhibitor (Fadrozole) on gonadal structures of mature females. Complete sex change was induced by 11-KT, 11-KA, and Fadrozole. Our results strongly suggest that an increase in 11-KT concentration and perhaps also a decrease in 17beta-E2 concentration are involved in mediating natural sex change in C. nicholsii.     

Mineral balance and whole body bone mineral content in very low-birth-weight infants

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants ( 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65±14 and 62±9mg/kg/day versus 55±12 and 47±7mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5±0.4 g/kg/day and 88±4% versus 4.2±1 g/kg/day, 79±6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3±30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6±36.6g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups. The deficit in the 12 subjects who had a BMCt under 30 g at 3 months of age had been corrected at age 6 months. Premature babies fed a pooled pasteurized human milk enriched with calcium, phosphorus and magnesium favored a better retention of calcium and phosphorus. However, no significant influence of the two diets studied was observed on the gain in BMCt over the first 6 months of life.     

Community based, effective, low cost approach to the treatment of severe malnutrition in rural Jamaica

Moderate and severe malnutrition are endemic in much of the developing world and in association with pockets of deprivation in the developed world. The cost in terms of individual and social development is high. The principles of effective management are clearly documented. A low cost, community based treatment programme for moderately and severely malnourished children under 3 years of age was established at a health centre in rural Jamaica. Children were followed up monthly and defaulters were rigorously recalled. Management consisted of carefully delivered dietary advice, antibiotics, anthelminthics, and vitamin supplements. All children improved and the response of 36 children, who were treated in the first year, showed an accelerated weight gain, with catch-up growth and the maintenance of length gain. There was a significant increase in the weight for age, at 1.9% per month over six months, which exceeds the rate reported with food supplementation programmes and nutrition rehabilitation centres.     

Selective cognitive processing of drug cues in heroin dependence

Previous studies provide evidence for the selective processing of disorder related stimuli on anxiety, depression, and eating disorders. There exist some preliminary indications that selective processing of drug cues may be involved in drug craving and relapse that deserve further investigation. In order to investigate the role of processing bias in an abnormal motivational system, the attentional bias for drug related stimuli was studied in a heroin dependent population. Heroin dependent participants (n = 21) and control participants (n = 30) performed a supra- and subliminal heroin Stroop task and heroin craving was assessed. Heroin dependent participants showed a considerable attentional bias for supraliminally presented heroin cues. However, there was no evidence for a preattentive bias on the subliminal presented cues. Reaction time on heroin cues was significantly predicted by heroin craving-levels. Results indicate that selective processing may be related to motivational induced states in general. The finding are discussed in the context of selective information processing in general psychopathology and in motivational processes as addiction specifically.     

Influence of individual differences in craving and obsessive cocaine thoughts on attentional processes in cocaine abuse patients

In the present pilot-study, the relation between craving, obsessive thoughts about cocaine, experienced control, and attentional bias for cocaine related words is investigated. Sixteen cocaine abuse patients participated in a reaction time (RT) experiment which was employed to measure the ability of subjects to shift their attention away from cocaine related words. Postexperiment craving was found to be positively correlated with reaction times on drug related cues, in contrast to RT on neutral cues. Furthermore, obsessive thoughts about cocaine use and the experienced cocaine use control, in the week before the experiment, were correlated in a higher degree with RTs on drug cues than postexperiment craving. Attentional bias for drug cues was evidenced in patients with higher scores on obsessive cocaine thoughts and higher craving scores. This study shows that individual differences on information processing, within a cocaine abuse patient population, are present.