Molecular genetics and transfusion management in a child with Bernard Soulier syndrome.

We present a case of Bernard Soulier syndrome in a 9-year-old boy caused by a novel genetic mutation. This child was shown to be homozygous for a single nucleotide deletion (c.1077delG) in the GP1BA gene not previously reported. Clinically, the boy has become refractory to platelet transfusions with both allo-antibodies and iso-antibodies and a massive transfusion requirement for ongoing haemorrhage. We describe the critical role that the blood product transfusion continues to play in the management of Bernard Soulier syndrome and discuss therapeutic options in these patients.     

In vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in rats

The in vivo action of insulin-like growth factor-I on bone metabolism has been studied using a new model. Insulin-like growth factor-I (IGF-I) was continuously infused into the arterial supply of the right hindlimb of ambulatory rats for up to 14 days and the effects on cortical and trabecular bone formation and the number of osteoclasts were determined by histomorphometric techniques. The contralateral limb acted as an internal control. IGF-I infusion significantly increased cortical bone formation (p less than 0.01). Trabecular bone was increased 22% (p = 0.07), but the infusion was only for seven days. These effects of IGF-I were age dependent, being absent in young, rapidly growing animals, but present at least until one year of age. IGF-I appears to be a purely anabolic hormone for bone formation, since it significantly stimulates osteoblasts and decreases the number of osteoclasts. Thus, although IGF-I mediates the growth-promoting effect of growth hormone, it does not mediate growth hormone's action on bone resorption.     

三种泻心汤及其类方不同配伍对正常大鼠胃粘液成分的影响

目的:探讨半夏泻心汤及其类方不同配伍对正常大鼠粘液含量的影响.方法:用均匀设计法对半夏泻心汤及其类方进行组方药量变化,以胃粘液含量为药理学指标,对所得的药理实验数据进行逐步回归分析.结果:与胃粘液含量关联度最大的为黄连,可以显著降低其含量,其次对半夏、大枣和甘草的交互项,可增加胃粘液含量.药物之间存在复杂的交互作用.结论:均匀设计为研究类方配伍提供了一种可供参考的试验设计方法.     

CD3ζ链基因在脐带血T细胞及其CD4+和CD8+T细胞亚群中的表达特点

目的 了解脐带血T细胞及其CD4 和CD8 T细胞亚群的信号传导分子CD3ζ基因的表达特点.方法 采用SYBR Green Ⅰ荧光定量PCR和相对定量分析法检测60例脐带血单个核细胞和12例纯化脐带血CD4 及CD8 T细胞的CD3ζ基因的表达情况,以β2微球蛋白基因(β2M)作为内参,采用相对定量公式:2-△Ct×100%,计算CD3ζ基因相对mRNA表达量,60例健康成人作为对照.并根据荧光定量PCR熔解曲线特点和序列分析了解CD3ζ基因突变情况.结果 全部脐带血和健康成人外周血单个核细胞均表达CD3ζ基因,不同个体CD3ζ基因表达量有所差异,脐带血T细胞CD3ζ基因相对mRNA表达量为6.7%±5.56%,CD4 和CD8 T细胞的CD3ζ基因相对mRNA表达量分别为6.74%±2.0%和6.88%±1.76%,三者CD3ζ基因表达量均明显高于健康成人(P=0.000,P=0.034,P=0.000).序列分析结果显示尚未发现国外文献所报道的ζ链剪接异构体.结论 本研究率先报道了脐带血T细胞及其CD4 和CD8 T细胞亚群的CD3ζ基因mRNA的表达水平,为进一步了解脐带血T细胞免疫学特点提供新的基础资料.     

Afferent innervation of the utricular macula in pigeons

Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were located in the extrastriola. The cellular organization and innervation patterns of the utricular maculae in birds appear to represent an organ in adaptive evolution, different from that observed for amphibians or mammals.     

Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.     

Beauveriolides, specific inhibitors of lipid droplet formation in mouse macrophages, produced by Beauveria sp. FO-6979

Beauveria sp. FO-6979, a soil isolate, was found to produce inhibitors of lipid droplet formation in mouse peritoneal macrophages. A new compound beauveriolide III was isolated along with a known compound beauveriolide I from the fermentation broth of the producing strain by solvent extraction, ODS column chromatography, silica gel column chromatography and preparative HPLC. Beauveriolides I and III caused a reduction in the number and size of cytosolic lipid droplets in macrophages at 10 microM without any cytotoxic effect on macrophages.     

人单核巨噬细胞泡沫化抑制剂筛选模型的建立及应用

目的: 建立人单核巨噬细胞泡沫化抑制剂筛选模型,筛选得到可抑制细胞泡沫化的抑制剂.方法: U937单核细胞经100 nmol·L-1佛波酯(PMA)诱导72 h分化为巨噬细胞后,换无血清培养液于96孔板中,每毫升含巨噬细胞1×106个,每孔再加入80 mg·L-1氧化的低密度脂蛋白(ox-LDL),37 ℃培养48 h,建立单核巨噬细胞泡沫化模型.利用微生物发酵液,或单一的化合物样品与其共孵育,油红.染色后观察细胞胞内变化,寻找对泡沫细胞形成有抑制作用的样品.利用基因工程技术表达的人清道夫受体A类II型的胞外部分,在本模型中可抑制巨噬细胞泡沫化的形成,进一步验证了模型的可行性.结果: 从2000 个微生物发酵液中筛选到6株微生物发酵液为阳性,从10个化合物中发现一个有抑制巨噬细胞泡沫化活性的新化合物.结论: 本模型可用于细胞泡沫化抑制剂的高通量筛选.