Antibodies to interleukin-1 inhibit cytokine-induced proliferation of neonatal rat Schwann cells in vitro

Unfractionated cytokines have been shown to induce in vitro proliferation of neonatal rat Schwann cells but the nature of the mitogen(s) is not known. A mixture of rabbit antibodies specific for recombinant interleukin-1α (IL-1α) and interleukin-1β (IL-1β) inhibited Schwann cell proliferation induced by unfractionated human cytokines whereas antibodies to interleukin-2 (IL-2) and control IgG did not. However, purified human IL-1 and recombinant human IL-1α or β did not induce Schwann cell proliferation on their own.     

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.     

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.     

锌剂在消化性溃疡中愈合作用的临床观察

目的 :为探讨锌剂在消化性溃疡 (Pu)的愈合作用 ,用依安欣治疗PU ,观察溃疡的愈合率、瘢痕 (S2 )的形成率以及临床症状缓解情况。方法 :研究组 70例 ,用依安欣 0 .3 g ,tid ,法膜替丁 2 0mg ,tid ,克拉霉素 0 .2 5 ,bid ,均为口服。对照组 3 6例 ,法膜替丁 2 0mg ,bid ,吉胃乐凝胶 2 0 g ,tid ,克拉霉素 0 .2 5 ,bid。疗程十二指肠溃疡 (DU ) ,均为四周 ,胃溃疡 (GU)六周 ,克拉霉素两组均为两周后停用 ,疗程结束后一周复查胃镜。结果DU治疗四周后的S2 形成率研究组和对照组分别为 69.7% (2 3 /3 3 )和 2 7.8% (5 /2 1) ,GU治疗六周后S2 形成率研究组和对照组分别为 70 % (2 1/3 0 )和 3 0 .8% (4 /13 ) ,两组分别比较存在显著性差异 (P <0 .0 5 ) ,两组DU和GU的愈合率及临床疗效均无明显差异 (P >0 .0 5 )。结论 :结果显示研究组的S2 形成率明显高于对照组 ,说明锌剂用于消化性溃疡治疗有明显促进胃粘膜愈合作用 ,同时配合抑酸剂更能提高溃疡愈合的质量。     

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。     

17β-雌二醇对大鼠脊髓损伤后神经保护作用的研究

目的：探讨17β-雌二醇（E2）对大鼠脊髓损伤（SCI）后的神经保护作用及其机制。方法：应用改良的Allen′s重物打击法建立大鼠急性脊髓损伤模型,将大鼠随机分为两组：A组（PBS对照组）和B组（E2治疗组）,每组42只,B组造模成功后15min及24h腹腔注射E2（4.0mg/kg,以PBS溶解）,A组在相同时间给予等量无菌PBS。分别于伤后7d、14d、21d及28d,应用改良Tarlov评分法和Rivlin斜板试验评价大鼠脊髓神经功能恢复情况。于伤后6h、24h、3d、7d、14d及28d时处死动物,以损伤部位为中心取材,HE染色观察脊髓组织病理变化,TUNEL法染色检测细胞凋亡,免疫组化染色检测caspase-3、Bcl-2的表达情况。结果：从伤后14d起,B组Tarlov评分和斜板试验角度与A组相比差异有显著性（P〈0.01）。TUNEL法检测表明,大鼠SCI后存在细胞凋亡,3d时达高峰,与caspase-3的表达基本一致,B组伤后24h、3d及7d时凋亡细胞比率显著低于A组（P〈0.01或P〈0.05）。免疫组化结果显示B组伤后24h、3d、7d、14d及28d时caspase-3表达低于A组（P〈0.01或P〈0.05）,而Bcl-2表达高于A组（P〈0.01或P〈0.05）。结论：E2能促进大鼠SCI后的神经功能恢复,具有一定的神经保护作用;E2可能是通过减少SCI后继发性细胞凋亡的机制发挥作用的。