Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population

Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is important for downregulation of T-cell activation, and CTLA-4 gene polymorphisms have been implicated as risk factors for rheumatoid arthritis (RA). Previous studies of the association between the +49 polymorphism of the CTLA-4 gene in RA have provided conflicting results. In order to determine association of the CTLA-4 gene with RA in Chinese Han population, we used denaturing gradient gel electrophoresis (DGGE) to genotype polymorphisms of four SNPs (MH30, +49, CT60 and JO31) of the CTLA-4 gene in 326 RA patients and 250 healthy controls. Furthermore, meta-analysis of all available studies relating +49 polymorphism to the risk of RA was performed to confirm the disease association. Among the SNPs examined, the genotype frequencies of CTLA-4 +49 and CT60 in RA patients differed significantly from controls (P=0.028 and 0.007). In addition, the distribution of four haplotypes constructed by these two SNPs was significantly different between patients and controls (chi(2)=10.58, d.f. =3, P=0.014). The meta-analysis also revealed that in both European and Asian populations, the CLTA-4 +49 G allele was associated with the risk of RA. These results suggested that the CTLA-4 gene might be involved in the susceptibility to RA in the Chinese Han population and both +49 and CT60 of CTLA-4 gene might be the causal variants in RA disease.     

Expression of CTLA-4 Molecule in Peripheral Blood T Lymphocytes from Patients with Systemic Lupus Erythematosus

CTLA-4 is a cell surface molecule expressed on activated T cells that is suggested to deliver a negative signal for T cell activation. Since CTLA-4 might be a negative regulator of autoimmune diseases, we investigated its expression on T cells from 20 patients with systemic lupus erythematosus (SLE) by flow cytometric analysis and RT-PCR. We found that although CTLA-4 mRNA was readily detected in all patients and controls, only a very minor subset of T cells expressed detectable surface CTLA-4 molecules in both groups. But patients with SLE had significantly increased percentages of CTLA-4-positive T cells compared with normal controls, implying at least that there was no apparent defective expression of CTLA-4 molecule in human lupus. The kinetics of CTLA-4 expression on T cells stimulated in vitro with PMA plus ionomycin were similar in normal controls and patients with SLE. The expression of CTLA-4 molecules after stimulation increased gradually and peaked at 72 hr. However, the induction of CTLA-4 expression on patients' T cells appeared to be weaker than that of normal individuals. Whether this reflects impaired down regulation by CTLA-4 molecules in SLE patients needs to be clarified further.     

Cloning and spatial and temporal expression of the zebrafish dopamine D1 receptor.

Dopamine plays important roles in the regulation of central nervous system (CNS) development and functions. In vertebrates, two families of dopamine receptors, collectively known as dopamine D1 and D2 receptors, have been identified. Recently, dopamine receptors have been targeted by pharmacological and therapeutic studies of neurological disorders, such as Parkinson's disease. Here, we report a study on the molecular characterization of dopamine D1 receptor in zebrafish (Danio rerio). We cloned the full-length cDNA of a zebrafish dopamine D1 receptor, designated as drd1. The sequence of drd1 shares high homology to the sequences of dopamine D1 receptors in mammalian, amphibian, and other fish species. drd1 is expressed in the CNS. The first drd1 expression was observed at approximately 30 hours postfertilization, at which time the expression was seen in the developing diencephalon and hindbrain. In developing retinas, the expression of drd1 was detected in the inner nuclear layer with the exception of the marginal zones. In adult retinas, drd1 expression was detected in most cell types in the inner and outer nuclear layers as well as ganglion cell layer. Differential expression of drd1 in developing and adult retinas may play various roles in regulating visual system functions.     

Effect of Group A Streptococcal Cysteine Protease on Invasion of Epithelial Cells

Cysteine protease of group A streptococci (GAS) is considered an important virulence factor. However, its role in invasiveness of GAS has not been investigated. We demonstrated in this study that two strains of protease-producing GAS had the ability to invade A-549 human respiratory epithelial cells. Isogenic protease mutants were constructed by using integrational plasmids to disrupt the speB gene and confirmed by Southern hybridization and Western immunoblot analyses. No extracellular protease activity was produced by the mutants. The mutants had growth rates similar to those of the wild-type strains and produced normal levels of other extracellular proteins. When invading A-549 cells, the mutants had a two- to threefold decrease in activity compared to that of the wild-type strains. The invasion activity increased when the A-549 cells were incubated with purified cysteine protease and the mutant. However, blockage of the cysteine protease with a specific cysteine protease inhibitor, E-64, decreased the invasion activity of GAS. Intracellular growth of GAS was not found in A-549 cells. The presence or absence of protease activity did not affect the adhesive ability of GAS. These results suggested that streptococcal cysteine protease can enhance the invasion ability of GAS in human respiratory epithelial cells.     

Pulmonary artery angiosarcoma: a clinicopathologic and radiological correlation

A 69-year-old man presented with cough, shortness of breath, and fatigue. He was initially treated for allergies and then for pulmonary embolism. Radiologically, a tumor mass was found to occlude the right pulmonary artery and involve the pulmonary trunk. A right pneumonectomy was performed. Histologically, a cellular malignant spindle and epithelioid tumor with areas of necrosis and brisk mitotic activity was seen. In some areas, the tumor appeared to form vascular channels. Focal osteosarcomatous differentiation was present. Immunohistochemical studies were performed including vimentin, smooth muscle actin, desmin, CD31, CD34, S100, and pan-cytokeratin. The tumor cells were positive for CD31 and vimentin and negative for pan-cytokeratin, CD34, and S100. Two months after surgery, the patient was alive and well.     

Pentasomy 8q in therapy-related myelodysplastic syndrome due to cyclophosphamide therapy for fibrosing alveolitis

Trisomy 8/8q is a common cytogenetic event in myelocytic malignancies, ranging from myelodysplastic syndrome (MDS) to acute myelocytic leukemia (AML) to blastic transformation of chronic myelocytic leukemia. Isochromosome 8q results in the same gene dosage effect. Duplication of i(8q), resulting in pentasomy 8q, has been reported only in two cases of AML. A patient with fibrosing alveolitis on prolonged cyclophosphamide treatment developed therapy-related MDS. Karyotyping, FISH, and CGH analysis showed a duplicated i(8q) among other complex abnormalities. The clinical features of 11 cases of myelocytic leukemia with pentasomy and hexasomy 8/8q were summarized. Compared with trisomy and tetrasomy 8, significant features included reduced median survival (90 days), treatment refractoriness (even with transplantation), monocytic differentiation, trilineage dysplasia, and radiation or toxin exposure. Increasing copy numbers of chromosome 8/8q may therefore be a marker of advanced leukemic evolution, exposure to toxins, underlying myelodysplasia, and an overall poor prognosis.     

Novel multi-component nanopharmaceuticals derived from poly(ethylene) glycol, retro-inverso-Tat nonapeptide and saquinavir demonstrate combined anti-HIV effects

Background  

Current anti-AIDS therapeutic agents and treatment regimens can provide a dramatically improved quality of life for HIV-positive people, many of whom have no detectable viral load for prolonged periods of time. Despite this, curing AIDS remains an elusive goal, partially due to the occurrence of drug resistance. Since the development of resistance is linked to, among other things, fluctuating drug levels, our long-term goal has been to develop nanotechnology-based drug delivery systems that can improve therapy by more precisely controlling drug concentrations in target cells. The theme of the current study is to investigate the value of combining AIDS drugs and modifiers of cellular uptake into macromolecular conjugates having novel pharmacological properties.     

Aperture modulated arc therapy

We show that it is possible to translate an intensity modulated radiation therapy (IMRT) treatment plan and deliver it as a single arc. This technique is referred to in this paper as aperture modulation arc therapy (AMAT). During this arc, the MLC leaves do not conform to the projection of the target PTV and the machine output of the accelerator has a constant value. Dose was calculated using the CORVUS 4.0 IMRT system, which uses a pencil beam dose algorithm, and treatments were delivered using a Varian 2100C/D Clinac. Results are presented for a head and neck and a prostate case, showing the equivalence of the IMRT and the translated AMAT delivery. For a prostate AMAT delivery, coronal plane film dose for the IMRT and AMAT deliveries agreed within 7.19 +/- 6.62%. For a meningioma the coronal plane dose distributions were similar to a value of 4.6 +/- 6.62%. Dose to the isocentre was measured as being within 2% of the planned value in both cases.     

模拟股骨置入人工关节扭转与应力松弛蠕变的实验研究

研究了在相同扭矩作用下,正常组股骨和以生物学和骨水泥固定置入人工关节组股骨标本扭转角度,还对正常股骨、生物学固定股骨和骨水泥固定股骨进行应力松弛、蠕变实验,为临床提供生物力学参数。以电子万能试验机对正常对照组、股骨置入人工关节骨水泥固定组、股骨置入人工关节生物学固定组标本进行扭转和粘弹性实验研究。得出了各组标本在相同扭矩下的扭转角度及悬臂弯曲状态下,正常组和置入人工关节组标本应力松弛、蠕变数据和曲线。对实验数据进行归一化处理,得出了正常组和置入人工关节组标本的归一化应力松弛函数,归一化蠕变函数及曲线。表明:骨水泥固定组扭转角比生物学固定组小,说明骨水泥固定有较好的稳定性,其应力松弛、蠕变量丢失小。骨水泥固定组较生物学固定组3600s应力松弛、蠕变量大。