肾上腺髓质素的分子生物学意义及对肾脏损伤的影响

0 引言 肾上腺髓质素(adrenomedullin,ADM)是一种从人嗜铬细胞瘤组织中分离纯化出的多肽,它在正常肾上腺髓质及源于肾上腺髓质的嗜铬细胞瘤中含量丰富.近年来发现ADM在肾脏功能调节方面起着重要作用,现对ADM的生物学特性、生物学作用及其对肾脏的作用进行概述.     

Students and tutors' social representations of assessment in problem-based learning tutorials supporting change

Background  

Medical programmes that implement problem-based learning (PBL) face several challenges when introducing this innovative learning method. PBL relies on small group as the foundation of study, and tutors facilitate learning by guiding the process rather than teaching the group. One of the major challenges is the use of strategies to assess students working in small groups. Self-, peer- and tutor-assessment are integral part of PBL tutorials and they're not easy to perform, especially for non experienced students and tutors. The undergraduate PBL medical programme was introduced in 2003, and after two years the curriculum committee decided to evaluate the tutorial assessment in the new program.     

Epidemiology of frequent attenders: a 3-year historic cohort study comparing attendance, morbidity and prescriptions of one-year and persistent frequent attenders

Background  

General Practitioners spend a disproportionate amount of time on frequent attenders. So far, trials on the effect of interventions on frequent attenders have shown negative results. However, these trials were conducted in short-term frequent attenders. It would be more reasonable to target intervention at persistent frequent attenders. Typical characteristics of persistent frequent attenders, as opposed to 1-year frequent attenders and non-frequent attenders, may generate hypotheses regarding modifiable factors on which new randomized trials may be designed.     

PDGFRB Promotes Liver Metastasis Formation of Mesenchymal-Like Colorectal Tumor Cells

In epithelial tumors, the platelet-derived growth factor receptor B (PDGFRB) is mainly expressed by stromal cells of mesenchymal origin. Tumor cells may also acquire PDGFRB expression following epithelial-to-mesenchymal transition (EMT), which occurs during metastasis formation. Little is known about PDGFRB signaling in colorectal tumor cells. We studied the relationship between PDGFRB expression, EMT, and metastasis in human colorectal cancer (CRC) cohorts by analysis of gene expression profiles. PDGFRB expression in primary CRC was correlated with short disease-free and overall survival. PDGFRB was co-expressed with genes involved in platelet activation, transforming growth factor beta (TGFB) signaling, and EMT in three CRC cohorts. PDGFRB was expressed in mesenchymal-like tumor cell lines in vitro and stimulated invasion and liver metastasis formation in mice. Platelets, a major source of PDGF, preferentially bound to tumor cells in a non-activated state. Platelet activation caused robust PDGFRB tyrosine phosphorylation on tumor cells in vitro and in liver sinusoids in vivo. Platelets also release TGFB, which is a potent inducer of EMT. Inhibition of TGFB signaling in tumor cells caused partial reversion of the mesenchymal phenotype and strongly reduced PDGFRB expression and PDGF-stimulated tumor cell invasion. These results suggest that PDGFRB may contribute to the aggressive phenotype of colorectal tumors with mesenchymal properties, most likely downstream of platelet activation and TGFB signaling.     

Relationship between Myopia and Optical Components - A Study among Chinese Hong Kong Student Population

Purpose: To establish the prevalence and severity of myopia among the Chinese Hong Kong students and to study the relationship between myopia and optical components.Methods;One thousand and seventy-five freshmen of the 1993-1994 academic year in the Chinese University of Hong Kong underwent the eye examination including evaluation of refractive error, keratometry, and A-scan ultrasonic biometry. The data were analyzed with the SPSS/PC 4. 01 statistical package. Results: The prevalence of myopia was 91. 7% with the mean refraction being -4. 00 ± 2. 64D in this young adult population. The statistical analyses demonstrated a significant correlation between refractive value and axial length of the globe (r=-0. 78), vitreous length (r=-0. 76), anterior chamber depth (r=-0. 33), lens thickness (r = 0. 13) and corneal curvature (r = 0. 19). Conclusion: The refractive status is mainly dependent on the axial length. In general, the higher the myopia was, the longer the eyeball, the deeper the anterior chamber,     

雷公藤三萜酸C的分离与结构鉴定

雷公藤总甙系雷公藤(Tripterygium wilfordii Hook.f)去皮根心经提取后得到的有效组分,它具有很强的抗炎免疫抑制作用。作者从雷公藤总甙中分离出5个三萜类化合物T_1,T_2,T_3,T_6,T_(28)。本文报道T_(28)化合物的分子结构,其他待另文发表。T_(28)是一个新的乌     

Minisatellite rearrangements are increased in liver tumours induced by transplacental aflatoxin B1 treatment of hepatitis B virus transgenic mice, but not in spontaneously arising tumours

Transgenic mice carrying an integrated subgenomic human hepatitis B virus (HBV) DNA fragment coding for the viral envelope polypeptides, represent a model for the study of the mechanisms involved in hepatocarcinogenesis. The mice develop a progressive liver injury characterized by inflammation, regenerative hyperplasia and dysplasia terminating in hepatocellular carcinoma (HCC) at around 18-21 months of age. No alterations in specific oncogenes and tumour suppressor genes in the HCC arising in this transgenic model have been observed. However, onset of liver tumours is significantly earlier in mice treated with aflatoxin B1 (AFB1). In order to examine more generally for genetic rearrangements during the natural history of the disease, DNA multilocus fingerprinting was performed using probes recognizing mouse minisatellites. Liver tumour samples from HBV transgenic mice either untreated or treated with AFB1 transplacentally were included in the study. In a total of 28 tumour samples from HBV transgenic mice receiving no carcinogen treatment, using three minisatellite probes, no alterations were detected. The frequency of rearrangements using any one of the three probes is calculated to be below 0.2%. This result demonstrates that genetic instability in minisatellite sequences is not a common event associated with HBV gene expression and liver injury in this model. In 11 liver tumours from mice exposed to AFB1 transplacentally six had minisatellite alterations (band gains and losses) revealed by at least one of the three probes used. The frequency of rearrangements was between 1.1% and 2% depending on the minisatellite probe. These data show that genetic alterations can be induced by transplacental exposure to AFB1 and suggest that genetic instability could be important in hepatocarcinogenesis with combined exposures to AFB1 and HBV.      

Involvement of PKCα and G-protein-coupled receptor kinase 2 in agonist-selective desensitization of μ-opioid receptors in mature brain neurons

Background and purpose:

The ability of an agonist to induce desensitization of the µ-opioid receptor (MOR) depends upon the agonist used. Furthermore, previous data suggest that the intracellular mechanisms underlying desensitization may be agonist-specific. We investigated the mechanisms underlying MOR desensitization, in adult mammalian neurons, caused by morphine (a partial agonist in this system) and DAMGO (a high-efficacy agonist).

Experimental approach:

MOR function was measured in locus coeruleus neurons, by using whole-cell patch-clamp electrophysiology, in rat and mouse brain slices (both wild-type and protein kinase C (PKC)α knockout mice). Specific isoforms of PKC were inhibited by using inhibitors of the receptors for activated C-kinase (RACK), and in vivo viral-mediated gene-transfer was used to transfect neurons with dominant negative mutants (DNMs) of specific G-protein-coupled receptor kinases (GRKs).

Key results:

Morphine-induced desensitization was attenuated by using RACK inhibitors that inhibit PKCα, but not by other isoform-specific inhibitors. Further, the PKC component of morphine-induced desensitization was absent in locus coeruleus neurons from PKCα knockout mice. The PKC-enhanced morphine-induced desensitization was not affected by over-expression of a GRK2 dominant negative mutant (GRK2 DNM). In contrast, DAMGO-induced MOR desensitization was independent of PKC activity but was reduced by over-expression of the GRK2 DNM but not by that of a GRK6 DNM.

Conclusions and implications:

In mature mammalian neurons, different MOR agonists can induce MOR desensitization by different mechanisms, morphine by a PKCα-mediated, heterologous mechanism and DAMGO by a GRK-mediated, homologous mechanism. These data represent functional selectivity at the level of receptor desensitization.