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.     

蛇床子水提取液抑瘤作用的实验研究

目的 :研究蛇床子水提取液的体内抗肿瘤作用。方法 :通过 S180 肉瘤移植建立荷瘤小鼠模型 ,给予不同剂量蛇床子水提取液后观察 S180 荷瘤小鼠肿瘤生长曲线、血清唾液酸 (SA)、瘤重及小鼠生存天数的变化。结果 :蛇床子水提取液能明显抑制肿瘤生长 ,降低荷瘤小鼠血清 SA水平 ,0 .0 6mg/(g· d) ,0 .1 1 mg/(g· d)、0 .2 1 mg/(g· d)剂量组平均瘤重低于肿瘤对照组 (P<0 .0 5 ) ,抑瘤率依次为 2 3 .2 %、2 9.1 %和 2 4 .8%,且能延长荷瘤小鼠生存天数 (P<0 .0 1 ) ,动物生命延长率依次为 :2 6 .9%、3 4 .8%和 2 6 .6 %。结论 :蛇床子水提取液具有较强的抗肿瘤效应 ,有很好的利用前景 ,值得对其进行深入研究。     

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.     

Herpes simplex virus latency in the nervous system – a new model

Permissive herpes simplex virus (HSV) infection in tissue culture results in host cell destruction. Latent HSV infection in vivo occurs in neurons of peripheral sensory ganglia (PSG) and it therefore can not take place in neurons in which the virus has completed a lytic replication cycle similar to that present in vitro. Our hypothesis, based on experimental data and observations in humans, suggests that establishment of latent infection and reactivation of HSV-1 does not involve neuronal cell loss. Latency is established in neurons in which the virus does not replicate and is determined, in part, by the tissue levels of a herpes transactivating protein (Vmw65) that is a component of the viral tegument. We also suggest that reactivation of latent infection does not involve destruction of neurons and is due to replication of virus at the peripheral mucocutaneous tissues to where virus or viral DNA have been transported from the nervous tissue. Alternatively, reactivation is initiated in the PSG using a replication cycle which does not involve irreversible damage to neurons. This model explains the lack of damage to neurons which continue to serve as permanent reservoirs of latent virus for the entire life of the host.     

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.     

The effect of interleukin-1 on iron metabolism in rats

The effect of interleukin-1 on iron metabolism in rats was evaluated. Plasma iron decreased from 184 +/- 16 micrograms/dl (mean +/- SE) to 24 +/- 12 at 6 hours after interleukin-1 intramuscular administration in non-fasting rats and 109 +/- 6 micrograms/dl to 12 +/- 1 micrograms/dl in fasting rats, which was significantly lower than in control rats. Ferrokinetic studies showed a more rapid disappearance rate and lower iron turnover in interleukin-1-injected rats. The release of iron from the mononuclear phagocyte system to plasma was studied at 3 h after interleukin-1 administration. Although the percent of radioactivity in plasma of the total injected dose was 3.2 +/- 0.6% in interleukin-1, which was significantly lower than in the control rats (5.4 +/- 0.6%) at 9 h after intravenous injection of 59Fe chondroitin ferrous sulfate, there was no difference between the amount of 59Fe released from the mononuclear phagocyte system over the first 9 h in interleukin-1 and control rats. These data appear to imply that iron release is unimpaired but that, for some reason, there is an enhanced rate of clearance of the 59Fe once it has been released from the mononuclear phagocyte system into the plasma.     

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.