Developing a model for clinical and basic science teaching skills

This report describes a model for identifying sets of teaching abilities considered to be effective for medical school teaching staff, based on roles teachers assume and functions they are expected to perform as instructors. The specification of these teaching abilities was the first step in the development of a comprehensive course on Medical Instruction at the Basic Institute of Medical and Agricultural Biology of the State University of Sao Paulo, Botucatu, Brazil, where the senior author is employed. The work was based on the assumption that medical school teachers are expected to assume a variety of teaching roles and that identification and specification of the abilities that define their roles can result in more effective and efficient teaching.     

Folding and function of the myelin proteins from primary sequence data.

To explain how the myelin proteins are involved in the organization and function of the myelin sheath requires knowing their molecular structures. Except for P2 basic protein of PNS myelin, however, their structures are not yet known. As an aid to predicting their molecular folding and possible functions, we have developed a FORTRAN program to analyze the primary sequence data for proteins, and have applied this to the myelin proteins in particular. In this program, propensities for the secondary structure conformations as well as physical-chemical parameters are assigned to the amino acids and the pattern of these parameters is examined by calculating their average values, autocorrelation functions and Fourier transforms. To compare two proteins, their sequences are aligned using a unitary scoring matrix, and homologies are searched by plotting a two-dimensional map of the correlation coefficients. Comparison of the corresponding myelin basic proteins (MBP) and P0 glycoproteins (P0) for rodent and shark showed that the conserved residues included most of the amino acids which were predicted to form the alpha or beta conformations, while the altered residues were mainly in the hydrophilic and turn or coil regions. In both rodent and shark the putative extracellular domain of P0 glycoprotein displayed consecutive peaks of beta propensity similar to that for the immunoglobulins, while the cytoplasmic domain showed alpha-beta-alpha folding. To trace the immunoglobulin fold along the P0 sequence, we compared the beta propensity curve of P0 with that of the immunoglobulin M603, whose three-dimensional structure has been determined. We propose that the flat beta-sheets of P0 are orientated parallel to the membrane surface to facilitate their homotypic interaction in the extracellular space. An extra beta-fold in the extracellular domain of shark P0 compared with rodent P0 was found, and this may result in a greater attraction between the apposed extracellular surfaces and may account for a smaller extracellular space as measured by x-ray diffraction. A computer search of the myelin protein sequences for functional motifs revealed sites for N-glycosylation, phosphorylation, nucleotide binding, and certain enzyme activities. We note especially that there are potential nucleotide binding sites in proteolipid protein (PLP), MBP and 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP). This is consistent with the experimental observations that PLP acts like an ionophore or proton channel when reconstituted into planar lipid bilayers, MBP binds GTP, and CNP catalyzes in vitro the hydrolysis of 2',3'-nucleotides into corresponding 2'-nucleotides.     

Multidrug transport in human glioblastoma cells is inhibited by transforming growth factors type beta 1, beta 2, and beta 1.2

The transforming growth factors type beta 1, beta 2, and beta 1.2 suppress multidrug transport in human pat-1 glioblastoma cells and even in cells that strongly over-express mdr genes and are resistant to inhibition of multidrug transport by chemosensitizers. Thus, inhibition of multidrug transport by cytokines might be a new approach to increase cellular accumulation of chemotherapeutic agents in multidrug resistant glial tumor cells. Interestingly, a member of the more distantly related decapentaplegic subgroup of transforming growth factors, the bone morphogenetic protein BMP 2, did not inhibit multidrug transport.     

二肽基肽酶Ⅳ抑制剂P32/98

二肽基肽酶Ⅳ(DPPⅣ)涉及2型糖尿病病理过程中的信号传导过程,其抑制剂能够增强胰岛素样多肽(GIP)和胰高血糖素样肽片段(GLP)的活性,并能提高葡萄糖耐受水平.动物实验研究表明,糖尿病模型大鼠口服DPPⅣ抑制剂P32/98,能降低DPPⅣ的活性,改善糖耐受性以及增加胰岛素的敏感性.临床试验进一步揭示,P32/98的安全性和耐受性良好,能明显改善受试者糖耐受性和胰岛素应答水平.     

Synthesis of deramciclane* labeled with tritium in various positions

[(1R)‐endo]‐(+)‐3‐bromocamphor was dehalogenated with tritium gas to [3‐³H]camphor and via [3‐³H]phenylborneol converted to [3‐³H]deramciclane isolated as the fumarate salt (specific activity 51.8 GBq/mmol). This three step synthesis from [3‐³H]camphor gave an overall yield of 22%. Benzyloxy‐acetic acid methyl ester was reduced with sodium‐borotritide to 2‐benzyloxy‐ethanol‐[1‐³H], and through a four step procedure was converted to 2‐dimethylaminoethyl‐[2‐³H] chloride. The latter was condensed with the sodium derivative of 2‐phenylborneol giving rise to [2‐dimethylamino‐[2‐³H]ethoxy]deramciclane isolated as the fumarate (specific activity 8.177 GBq/mmol). This six step synthesis from [³H]NaBH₄ gave an overall yield of 6%. Copyright © 2005 John Wiley & Sons, Ltd.     

CO2 reactivity and autoregulation in fetal brain

Intraventricular hemorrhage (IVH) in preterm infants is well known to be associated with the high morbidity and mortality of this group. Previous studies have suggested altered cerebral blood flow (CBF) as an important pathologic factor. We measured the CBF in nearterm rabbit fetuses using the hydrogen clearance technique. The local CBF of the rabbit fetuses was significantly low compared with that of the maternal rabbits. The response of CBF to changes in PaCO₂ was observed in rabbit fetuses. The CO₂ reactivity index of the fetal rabbit was lower than that of the maternal rabbit. This low CO₂ reactivity might reflect the immaturity of the fetal brain and its low CBF. We were unable to monitor the fetal blood pressure, but the fetal CBF remained stable when the maternal blood pressure was altered. It is well known that IVH in preterm infants originates from the subependymal germinal matrix and that this has many fragile vessels. Our observation suggests that even a small increase of CBF during hypercapnia might have a large effect towards producing hemorrhage.     

Immunoregulatory Factor Released From a Cell Line Derived From Human Decidual Tissue

ABSTRACT: The culture supernatant of the TTK-1 cell line, established from human decidual tissue, was found to contain a factor that strongly suppressed the mixed lymphocyte reaction (MLR). The mechanism of the MLR-suppressive activity as well as the biochemical characterization of this factor was analyzed. The TTK-1 supernatant suppressed the MLR much more strongly than the culture supernatants of the three other malignant cell lines examined. The molecular weight of this factor was estimated to be between 43 kilodaltons (kd) and 67 kd by gel filtration chromatography. The TTK-1 supernatant also suppressed the proliferation of the interleukin 2 (IL-2)-dependent T cell lines, but did not suppress that of the IL-2-independent T cell lines, suggesting that the TTK-1 supernatant inhibited the action of IL-2 and subsequently suppressed the MLR. The fact that the TTK-1 cell line originated from human decidual tissue might imply the important role of this factor in immunological fetomaternal balance.     

虚拟现实技术在枢椎椎弓根螺钉精确植入中的应用研究

目的探索以虚拟现实技术为基础的枢椎椎弓根螺钉置人方法。方法选取8具成人颅一颈椎标本，采用改良四柱式定位框架固定于枕颈，使颅-颈-肩形成统一刚体，保持空间位置恒定，CT薄层扫描获取枢椎三维定位信息，采用Aero—Tech立体定向手术规划系统三维建模，设计安全、可视化、个体化的虚拟置钉路径，反复虚拟演示验证钉道安全后，导向弓把持下置人导向钢针，复查CT评价置钉的准确性。结果16个枢椎椎弓根置钉过程中，方向出现偏差（横突孔突破）1个，失败率为6．25％。结论目标椎弓根的容积三维重建、置钉路径可视化设计和虚拟演示，使操作过程简单、直观而精确，不需要线形和角性参数的测量；加上导向抓持装置提供的稳定性，使该技术具有很好的临床应用前景。     

Special needs of adolescent and young women in accessing reproductive health: promoting partnerships between young people and health care providers.

This article considers the unique challenges and opportunities that health care providers (HCPs) face when they address the sexual and reproductive health and rights of young women accessing services. Some of the difficulties that HCPs encounter in their work are highlighted, including poor remuneration, the impact of their personal biases and the effect of an under-equipped working environment. The financial, logistical and emotional challenges young people face in accessing services are also described, as well as some small changes that could promote fruitful partnerships between HCPs and their young clientele. Also considered is how international documents concerning reproductive health can be utilized as advocacy tools to ensure that, when governments speak of making young people's needs a priority, resources are also made a priority-so that reproductive health can become a reality for all young people.     

端粒酶逆转录酶、环氧化酶-2在乳腺癌中的表达及其意义

目的 探讨端粒酶逆转录酶(hTERT)和环氧化酶(cox)-2在乳腺浸润性导管癌中的表达及其临床意义.方法 使用免疫组织化学法分别检测45例乳腺浸润性导管癌和22例乳腺良性病变标本的hTERT和COX-2蛋白表达情况.结果 hTERT在乳腺浸润性导管癌中阳性表达率fig71.11%,明显高于乳腺良性病变9.09%,两者比较差异有统计学意义(P<0.05).hTERT阳性表达与乳腺浸润性导管癌患者的年龄、肿瘤大小、腋窝淋巴结转移情况及雌、孕激素表达水平无相关性(P>0.05),与Her-2表达存在显著相关性(P<0.05).COX-2在乳腺浸润性导管癌中的阳性表达率为82.22%,明显高于乳腺良性病变50.00%,两者比较差异有统计学意义(P<0.05).COX-2阳性表达与乳腺浸润性导管癌患者腋窝淋巴结转移情况、Her-2、ER阳性表达有关(P<0.05).在乳腺浸润性导管癌中hTERT阳性表达与COX-2阳性表达呈正相关(r=0.557,P<0.01).结论 hTERT与COX-2在乳腺浸润性导管癌中的表达显著高于在乳腺良性病变中的表达,hTERT与COX-2在乳腺癌的发生、发展中起重要作用.hTERT表达与COX-2表达存在显著相关性,COX-2的过度表达可能是端粒酶激活和调节的机制之一.