流行性乙型脑炎病毒活疫苗株SA14-14-2基因稳定性研究

目的 通过研究流行性乙型脑炎活疫苗减毒株基因稳定性，从分子水平证实流行性乙型脑炎活疫苗的遗传稳定性。方法分析流行性乙型脑炎活疫苗主种子、工作种子及其相应的疫苗病毒E蛋白基因核苷酸和氨基酸序列，并与其强毒株和基因库中乙脑病毒减毒株(AF15119)比较。结果乙脑活疫苗主种子、工作种子及其相应的疫苗病毒的E蛋白基因核苷酸序列完全相同。这些病毒E蛋白的氨基酸序列与基因库中乙脑病毒弱毒株(AF315119)比较显示第E447位点氨基酸有差异。结论乙脑病毒活疫苗减毒株遗传学特性稳定。     

脑缺血再灌流对大鼠海马FOS蛋白的诱导及电针对其的影响

目的　探讨脑缺血再灌流后电针对大鼠海马FOS蛋白表达的影响。方法　采用夹闭大鼠双侧颈总动脉造成的脑缺血再灌流损伤模型 ,电针“百会”、“风池”、“大钟”及“足三里”穴 ,频率 2～ 2 0Hz,强度以肌肉轻微抖动为准 ,持续 30min ,4h后观察海马FOS蛋白的表达。结果　电针能明显加强脑缺血再灌流后海马各区FOS蛋白的表达。结论　缺血再灌流可诱导海马FOS蛋白的显著表达 ;电针信息对缺血后海马神经元的功能可能会有影响。     

Frequent expression of the multi-drug resistance-associated protein BCRP/MXR/ABCP/ABCG2 in human tumours detected by the BXP-21 monoclonal antibody in paraffin-embedded material

The expression and cellular localization of angiotensin II (Ang II) and AT(1) receptor proteins were examined in the normal human prostate and benign prostatic hyperplasia (BPH) by immunohistochemistry. In the normal prostate, Ang II immunoreactivity was localized to the basal layer of the epithelium and AT(1) receptor immunostaining was found predominantly on stromal smooth muscle and also on vascular smooth muscle of prostatic blood vessels. Ang II immunoreactivity was markedly increased in hyperplastic acini in BPH compared with acini in the normal prostate (normal: 7.4+/-0.2%, n=5 vs. BPH: 22.7+/-1.9%, n=5, p<0.001). However, AT(1) receptor immunoreactivity was significantly decreased in BPH compared with the normal prostate [normal: 16.4+/-2.2%, n=4 vs. BPH: 9.4+/-1.3%, n=5, p<0.05 (p=0.025)]. The present study demonstrates the presence of Ang II peptide in the basal layer of the epithelium and AT(1) receptors on stromal smooth muscle, suggesting that Ang II may mediate paracrine functions on cellular growth and smooth muscle tone in the human prostate. Furthermore, AT(1) receptor down-regulation in BPH may be due to receptor hyperstimulation by increased local levels of Ang II in BPH. These data extend previous findings in support of the novel concept that overactivity of the renin-angiotensin system (RAS) may be involved in the pathophysiology of BPH.     

Mutation analysis of PEX7 in 60 probands with rhizomelic chondrodysplasia punctata and functional correlations of genotype with phenotype

PEX7 encodes the cytosolic receptor for the set of peroxisomal matrix enzymes targeted to the organelle by the peroxisome targeting signal 2 (PTS2). Mutations in PEX7 cause rhizomelic chondrodysplasia punctata (RCDP), a distinct peroxisome biogenesis disorder. In previous work we described three novel PEX7 mutant alleles, including one, L292X, with a high frequency due to a founder effect. We have now extended our analysis to 60 RCDP probands and identified a total of 24 PEX7 alleles, accounting for 95% of the mutant PEX7 genes in our sample. Of these, 50% are L292X, 13% are IVS9+1G>C, and the remainder are mostly private. IVS9+1G>C occurs on at least three different haplotypes and thus appears to result from recurrent mutation. The phenotypic spectrum of RCDP is broader than commonly recognized and includes minimally affected individuals at the mild end of the spectrum. To relate PEX7 genotype and phenotype, we evaluated the consequence of the disease mutation on PEX7 RNA by Northern analysis and RT/PCR. We evaluated the function of the encoded Pex7 protein (Pex7p) by expressing selected alleles in fibroblasts from RCDP patients and assaying their ability to restore import of a PTS2 marker protein. We find that residual activity of mutant Pex7p and reduced amounts of normal Pex7p are associated with milder and variant phenotypes.     

Craniosynostosis in Twist heterozygous mice: A model for Saethre‐Chotzen syndrome

Saethre‐Chotzen syndrome is a common autosomal dominant form of craniosynostosis, the premature fusion of the sutures of the calvarial bones of the skull. Most Saethre‐Chotzen syndrome cases are caused by haploinsufficiency for the TWIST gene. Mice heterozygous for a null mutation of the Twist gene replicate certain features of Saethre‐Chotzen syndrome, but have not been reported to exhibit craniosynostosis. We demonstrate that Twist heterozygous mice exhibit fusions of the coronal suture and other cranial suture abnormalities, indicating that Twist heterozygous mice constitute a better animal model for Saethre‐Chotzen syndrome than was previously appreciated. Anat Rec 268:90–92, 2002. © 2002 Wiley‐Liss, Inc.     

Presence of antibodies to replication protein A in some patients with systemic lupus erythematosus (SLE)

Presence of antibodies directed against replication protein A (RPA), a DNA binding protein complex composed of three subunits (RPA-70, RPA-32 and RPA-14) was investigated among patients with SLE and other autoimmune diseases using immunoblot analysis to RPA-70 and RPA-32 recombinant proteins. Anti-RPA antibodies were found in two out of 108 sera from SLE patients, one of them showing reactivity against RPA-32 and RPA-70 and the other reacting only against RPA-32. Sera from 108 patients with other autoimmune disorders as well as from 42 healthy control individuals were negative. Thus, the frequency of these antibodies in SLE is estimated to be 2–3%. The study demonstrates that RPA is one target more of the wide array of autoantigens that elicit an immune response in SLE. The presence of anti-RPA autoantibodies seems to be circumscribed to a small number of patients with SLE.     

Gastric mucosal lesions caused in rats of different strains by emotional stress,and the protective effect of interleukin 1β

Acute emotional stress results in damage to gastric mucous membranes in August, Wag, and particularly Wistar rats. The damage is less severe in rats preinjected with inter-leukin 1β into a lateral ventricle of the cerebrum. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 117, N ^o 3, pp. 238–239, March, 1994     

Amelioration of established murine collagen-induced arthritis with anti-IL-1 treatment.

Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis. To validate a key role for IL-1 in arthritic processes we have studied the protective effect of neutralizing antimurine IL-1 antibodies in the murine collagen-induced arthritis (CIA) model. Combination of anti-IL-1 alpha and anti-IL-1 beta given before onset of arthritis was shown to prevent disease completely. Remarkably, a single treatment was also highly effective in the established phase of arthritis, reducing both inflammation as well as cartilage destruction. Suppression was most pronounced with the combination, but anti-IL-1 beta alone also induced significant relief. Finally, we studied the protective effect of IL-1 neutralization on cartilage metabolism in a unilateral expression model of collagen arthritis. To this end zymosan was injected in one knee joint before onset of disease, resulting in accelerated expression in that particular joint and the draining paw. Anti-IL-1 treatment started after accelerated expression of arthritis was able to fully normalize chondrocyte synthetic function, which was highly suppressed in the control group. It is concluded that IL-1 is an important determinant in both inflammation and cartilage destruction in collagen arthritis, and this may have implications for therapy in human arthritis.     

Townes-Brocks syndrome

Townes-Brocks syndrome (TBS) is an autosomal dominant disorder with multiple malformations and variable expression. Major findings include external ear anomalies, hearing loss, preaxial polydactyly and triphalangeal thumbs, imperforate anus, and renal malformations. Most patients with Townes-Brocks syndrome have normal intelligence, although mental retardation has been noted in a few.     

Prostaglandin E1 suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage-dependent glomerulonephritis.

Prostaglandin E1 (PGE1) suppresses macrophage infiltration and ameliorates injury in an experimental model of macrophage dependent glomerulonephritis. Macrophages are mediators of glomerular injury in models of proliferative glomerulonephritis. We have recently shown that macrophages in glomerulonephritis have low prostaglandin E2 (PGE) generation, and other evidence implicates eicosanoids as regulators of macrophage activation. Here we have studied in rats the effect of 15(s)-15-methyl PGE1 (M-PGE1) on accelerated nephrotoxic nephritis, a model of acute macrophage-dependent glomerular injury. M-PGE1 ameliorated proteinuria (day 4; 61 +/- 13 mg/24 h, n = 9; vehicle treated, 164 +/- 17 mg/24 h, n = 11; P less than 0.002) and glomerular hypercellularity; quantification of infiltrating macrophages by isolating glomerular cells showed reduction in the numbers of macrophages (44 +/- 9/glomerulus; vehicle treated, 119 +/- 15/glomerulus; P less than 0.02) with inhibition of Ia antigen expression on infiltrating macrophages (8 +/- 5%; vehicle treated 25 +/- 4% P less than 0.05). Glomerular binding of nephrotoxic globulin and levels of autologous antibodies were not affected by M-PGE1. Thus the mechanism of suppression involves inhibition of macrophage accumulation and activation. M-PGE1 administered to normal rats did not affect numbers of resident leucocytes (12.6 +/- 1.5/glomerulus; vehicle treated, 13.2 +/- 1.3/glomerulus) or alter Ia antigen expression (4.1 +/- 0.2 Ia + cells/glomerulus; vehicle treated, 3.9 +/- 0.6/glomerulus). This study suggests a therapeutic role for PGE1 in this type of glomerulonephritis, and has implications for the pathophysiology of macrophage-mediated inflammation.