CYP2D6和GST在白种人晚期肾病中的遗传变异

目的生物转化酶细胞色素P4502D6(CYP2D6)和谷胱苷肽转移酶-M1(GST-M1)、谷胱苷肽转移酶-T1(GST-T1)共同代谢内源性和外源性毒素,一部分人群由于相应基因变异导致这些酶缺乏表达,我们检测白种人群中晚期肾病(ESRD)病人这些酶的基因多态性是否比健康者有较高的频率.方法从列克星顿及周围地区征募330名晚期肾病病人和303名健康者,均为白种人,给予他们进行CYP2D6和GST-M1和T1基因分型.结果在ESRD病人中CYP2D6和GST-M1和GST-T1以及CYP2D6和GST-M1或GST-T1都缺乏分别为2.1%和4.2%;而在健康者中均为0.3%(P<0.01).结论CYP2D6和GST-M1和/或GST-T1酶缺乏在ESRD病人中有较高的频率,提示这些酶缺乏可以预计慢性肾病进展的可能性.     

Overexpression/amplification of HER-2/neu is uncommon in hepatocellular carcinoma

Background： Hepatocellular carcinoma （HCC） is one of the most prevalent fatal cancers in the world. Despite advances in early diagnosis and improvements in surgical techniques, the survival of patients with HCC even after resection is poor because of the high incidence of recurrences. Therefore, the identification of prognostic factors may be helpful in the development of new treatment protocols. Aims： To investigate HER-2/neu status in HCC by immunohistochemistry （IHC） and fluorescence in situ hybridisation （FISH）, and to explore the possibility of using trastuzumab in the treatment of HCC. Methods.. Eight hundred and sixty eight surgical samples from patients with primary HCC were examined for their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The correlations between HER-2/neu overexpression and clinicopathological characteristics were analysed statistically. Results： HER-2/neu overexpression was detected in 21 （2.42%） of the 868 primary HCCs. Only one specimen showed HER-2/neu gene amplification by FISH. No significant associations were found between HER-2/neu overexpression and the clinicopathological parameters. Conclusions： There is a low frequency of HER-2/neu overexpression/amplification in HCC. There appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti-HER-2/neu trastuzumab treatment in patients with HCC.     

Chronic expression of P-selectin on endothelial cells stimulated by the T-cell cytokine, interleukin-3

P-selectin expressed on the surface of endothelium mediates leukocyte adhesion in vitro and rolling in vivo. Several inducers of cell-surface P-selectin expression on endothelial cells (EC) have previously been identified, all of which yield transient cell-surface expression of P- selectin lasting minutes to a few hours. We now show that a T- lymphocyte product, interleukin-3 (IL-3), stimulates the long-term endothelial cells (HUVEC). IL-3 induced cell-surface P-selectin expression in two phases. An initial peak at 10 minutes was followed by a prolonged upregulation beginning 16 hours after IL-3 addition and lasting at least 4 days. The level of P-selectin expression induced by IL-3 added for 48 hours was similar to that induced by treatment of HUVEC for 10 minutes with thrombin, and the effect of adding IL-3 for 48 hours followed by thrombin for 10 minutes was additive. Induction of cell-surface P-selectin expression by IL-3 was blocked by pretreatment of EC with a blocking monoclonal antibody against the IL-3 receptor alpha-chain. Lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF alpha) and a mutant form of IL-3 with decreased potency did not induce cell-surface P-selectin expression after 48 hours' incubation with HUVEC, suggesting that the effect was specific to IL-3. The increase in cell-surface P-selectin expression occurring after 16 hours of incubation with IL-3 was accompanied by a similar prolonged increase in the steady-state mRNA level that was not observed at 10 minutes after IL-3 addition. As T-lymphocyte infiltration is a hallmark of chronic inflammation, our observations suggest that the secretion of IL-3 by T lymphocytes may serve to maintain the inflammatory state during chronic inflammation.     

Cutaneous polyarteritis nodosa in a child and a review of the literature

The cutaneous form of polyarteritis nodosa in children is extremely rare. Findings are usually limited to the skin, muscles and joints. It has a benign but often chronic course. We describe an 8-y-old girl with cutaneous PAN, with extensive livedo reticularis on lower and upper extremities, tender subcutaneous nodules, arthralgia and right ankle swelling. Skin biopsy revealed vasculitis of small and medium-sized blood vessels characterized by fibrinoid necrosis. The use of prednisolone resulted in clinical improvement initially, but recurrence occurred during tapering. She showed marked improvement with additional high dose methyl prednisolone monthly.     

View-invariant representations of familiar objects by neurons in the inferior temporal visual cortex

A view-invariant representation of objects in the brain would have many computational advantages. Here we describe a population of single neurons in the temporal visual cortex (IT) that have view-invariant representations of familiar objects. Ten real plastic objects were placed in the monkeys' home cages for a period of time before neurophysiological experiments in which neuronal responses were measured to four views of each object. The macaques performed a visual fixation task, and had never been trained in object discrimination. The majority of the visual neurons recorded were responsive to some views of some objects and/or to the control stimuli, as would be expected from previous studies. However, a small subset of these neurons were responsive to all views of one or more of the objects, providing evidence that these neurons were coding for objects, rather than simply for individual views or visual features within the image. This result was confirmed by information theoretic analyses, which showed that the neurons provided information about which object was being seen, independently of the view. The coding scheme was shown to be sparse distributed, with relatively independent information being provided by the different neurons. Hypotheses about how these view-invariant cells are formed are described.