周期性压力作用下椎间盘细胞中整合素α3的表达

目的 探讨整合素在体外培养的椎间盘细胞力学传导中的作用。方法采用猪的椎间盘进行体外细胞的分离和培养，对细胞施加周期性液压负荷，通过对细胞的形态学观察、Western免疫印迹、免疫细胞化学染色和免疫荧光，分别检测整合素α3和肌动蛋白在周期性压力下椎间盘细胞中的表达。结果经加压后，纤维环细胞和髓核细胞均可见体积缩小，由多角形转变为细长形，α3和肌动蛋白在AF和NP细胞中的表达均明显减少。结论压力抑制了整合素α3的产生，整合素α3将力的信号转换到细胞内时，进一步影响到与其关系密切的肌动蛋白。     

恶性肿瘤靶向给药的临床应用

恶性肿瘤靶向给药是指利用具有一定肿瘤靶向性的导向分子（载体）携带治疗肿瘤的药物,在肿瘤局部选择性杀伤肿瘤细胞（及转移的肿瘤细胞）,以避免药物的全身毒副作用,提高疗效的一种治疗方法．由于抗癌药物在杀伤肿瘤细胞的同时也杀伤正常细胞,增加了全身的毒副作用．因此,近几年来,对恶性肿瘤靶向治疗的研究突飞猛进,发展了人源性抗HER-2mAb、依西美坦、放射性核素、     

Man’s best friend? Infective endocarditis due to Capnocytophaga canimorsus

Infective endocarditis caused by zoonotic microorganisms is an uncommon clinical entity. A 55-year-old man was diagnosed with endocarditis due to Capnocytophaga canimorsus, a commensal bacterium contained in the saliva of dogs, that involved the aortic and tricuspid valves and was complicated by a para-aortic valve abscess and aorta-to-right atrial fistula. The patient was successfully treated with antibiotic therapy and surgical intervention. C canimorsus endocarditis should be considered in patients with culture-negative endocarditis, particularly in immunosuppressed, asplenic or alcoholic individuals who have recently suffered a dog bite or have had close contact with dogs.     

Colposcopic genital findings in prepubertal girls assessed for sexual abuse

After the introduction of the colposcope for the examination of children suspected of being sexually abused in Leeds, a study was undertaken to describe the findings in detail. A total of 109 consecutive prepubertal girls, mean age 70.4 months were assessed including colposcopic genital and anal examination, and peer group review of reports and photographs. Fifty nine children had signs consistent with blunt force penetrating trauma (hymenal transection/major notch, scar, or hymenal attenuation). Transections were encountered most commonly at 6 o'clock (directly posterior). In 46 the hymenal orifice was gaping with thigh abduction only and in 47 the hymenal orifice transverse diameter was greater than 4 mm on labial separation. Overall, physical findings were commonly present and in only two cases were no signs recorded. Non-specific and frequent findings included patterns of labial and introital reddening. Supportive hymenal signs including swelling, rounding of edge, thickening, distortion, and loss of symmetry were common. Labial fusion was present in 20. Urethral dilatation with labial separation was noted in 14. Physical findings including normality are consistent with abuse and even minor anogenital signs as well as negative findings should be documented. Colposcopy and photography are valuable tools in peer review, teaching, and case management.     

Radiological evidence of constipation in urinary tract infection

Little objective evidence has been published to support the claim that constipation is an important contributory factor in recurrent urinary tract infection (UTI) in childhood. Using a radiological scoring system, two observers assessed faecal loading from abdominal radiographs of children with proved UTIs. There was a significant increase in the degree of faecal loading in children with UTI when compared with controls (r = 0.237). This difference was mainly accounted for by girls with recurrent (greater than five) UTIs. This study confirms an association between recurrent UTI and faecal loading. Further studies are needed to establish if there is a causal relationship and benefits from treatment.     

Sustained activation of the extracellular signal-regulated kinase pathway protects cells from photofrin-mediated photodynamic therapy

Photodynamic therapy (PDT) is a cancer therapy in which a photosensitizer selectively accumulates in tumor cells and is subsequently activated by light of a specific wavelength. The activation of the photosensitizer leads to cytotoxic photoproducts that result in tumor regression. PDT can lead to several cellular responses including cell cycle arrest, necrosis, and apoptosis, as well as trigger many signaling pathways. It has been suggested that extracellular signal-activated protein kinases (ERKs), one subfamily of mitogen-activated protein kinases, play a crucial role in the cellular response to radiation therapy and chemotherapy. However, the role of ERKs in the cell survival after PDT is less clear. We have examined the response of the extracellular signal-regulated kinase ERK1/2 in PDT-resistant (LFS087) and PDT-sensitive (GM38A) cells after Photofrin-mediated PDT. ERK1/2 activity was induced rapidly in both cell types after PDT. The PDT-induced ERK1/2 activity was transient in GM38A cells and by 3 h had returned to a level significant lower than basal levels, whereas the induction of ERK1/2 was sustained in LFS087 cells and lasted for at least 11 h. Blocking of the sustained ERK activity with PD98059, an inhibitor of mitogen-activated protein/ERK kinase, significantly decreased cell survival of LFS087 after PDT. PDT also induced the expression of mitogen-activated protein kinase phosphatase, MKP-1, but reduced Raf-1 protein levels in both cell types. In GM38A cells, the substantially induced levels of MKP-1 correlated with the transient activation of ERK1/2 by PDT, and both basal and induced levels of MKP-1 were substantially greater in GM38 compared with Li Fraumeni syndrome cells. These observations suggest that sustained ERK1/2 activation protects cells from Photofrin-mediated phototoxicity and that the duration of ERK1/2 activation is regulated by MKP-1. In addition, the activation of ERK1/2 by Photofrin-mediated PDT is Raf-1 independent.     

Breast cancer risk associated with different HRT formulations: a register-based case-control study

Background  

Previous epidemiological studies have inconsistently shown a modestly increased breast cancer risk associated with hormone replacement therapy (HRT). Limited information is available about different formulations - particularly concerning different progestins.