Reproductive genetic counselling in non-mosaic 47,XXY patients: implications for preimplantation or prenatal diagnosis: Case report and review

With an incidence of approximately 1 in 500 male newborns, the 47,XXY genotype is one the most common sex chromosome anomalies. It is also the most frequent genetic cause of human infertility. Some non-mosaic 47,XXY patients have sperm production which allows infertility treatment to be offered by ICSI. Therefore, the risk of transmitting a chromosome anomaly to the next generation is an important problem in reproductive genetic counselling of these patients. Here, we report on a twin pregnancy where two karyotypically normal neonates 46,XX and 46,XY were born after the use of ICSI in assisted reproduction of a patient with a non-mosaic 47,XXY syndrome. To date, only 38 evolving pregnancies including the present cases, have been reported after ICSI using sperm from non-mosaic 47,XXY patients. Although these data are scarce, they suggest that the risk of chromosome anomaly in the offspring of these patients is low; hence, their reproductive genetic counselling can be reassuring, and management of the pregnancy can proceed with caution.     

Association between attention deficit hyperactivity disorder and the DXS7 locus

Attention deficit hyperactivity disorder (ADHD) is a prevalent disorder in children. The etiology of this disease is not clear. Genetics studies have suggested the involvement of the dopamine DRD-4 receptor gene and dopamine transporter gene (DAT1). Clinical studies have shown that monoamine oxidase-B (MAO-B) inhibitors are effective in the treatment of ADHD. These findings suggest that monoamine oxidase (MAO) genes might be involved in the origin of ADHD. In the present work, the DXS7 locus of chromosome X, which is closely linked to MAO genes, was selected as a marker to study the possible association between ADHD and MAO genes in the Chinese population. Haplotype-based haplotype relative risk (HHRR) and the transmission disequilibrium test (TDT) methods were employed to analyze the association and the linkage disequilibrium, respectively. Significant association (X(2) = 15.86; 1 df; P < 0.001) and linkage (X(2) = 14.88; 1 df; P < 0.001) were detected between the 157-bp allele of the DXS7 locus and the DSM-III-R-diagnosed ADHD (N = 72) in trios composed of father, mother, and affected offspring. The data suggested that ADHD was associated and in linkage with DXS7 locus.     

Bacterial superantigen-treated intestinal epithelial cells upregulate heat shock proteins 25 and 72 and are resistant to oxidant cytotoxicity

While the pathological events evoked by infection are commonly described, effective host responses to bacteria and their products should primarily be protective. Heat shock protein (Hsp) expression is upregulated by many stimuli and serves to maintain intracellular protein integrity. The ability of the prototypic superantigen, Staphylococcus aureus enterotoxin B (SEB) to induce Hsps was investigated with BALB/c mice and by in vitro addition to the murine small intestinal epithelial cell line MSIE. SEB-treated (5 or 100 microg intraperitoneally) mice revealed increased Hsp25 and Hsp72, but not Hsc73, in jejunal lymphocytes and epithelial cells. A similar Hsp response to SEB occurred in MSIE cells and was preceded by activation of the ERK1/2 and p38 mitogen-activated protein kinases but not the SAPK/JNK pathway; pharmacological inhibition of ERK1/2, but not p38, significantly reduced SEB-induced Hsps. Moreover, SEB-treated MSIE cells were protected against oxidant-induced cytotoxicity (measured by 51Cr release) and F-actin depolymerization. Thus, SEB exposure results in a rapid induction of the Hsp25 and Hsp72 in intestinal epithelial cells, both directly and through lymphocyte activation, and we suggest that this event is important in protecting the gut from damage by Staphylococcus infection or in the reparatory process and may be a generalized response to lumen-derived bacterial toxins.     

Synergistic antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of Vibrio vulnificus infection.

BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections.     

The carboxyl terminus of the epithelial Ca(2+) channel ECaC1 is involved in Ca(2+)-dependent inactivation

The family of epithelial Ca(2+) channels (ECaC) is a unique group of highly Ca(2+)-selective channels consisting of two members, ECaC1 and ECaC2. We used carboxyl terminal truncations and mutants to delineate the molecular determinants of the Ca(2+)-dependent inhibition of ECaC. To this end, rabbit ECaC1 was expressed heterologously with green fluorescent protein (GFP) in human embryonic kidney 293 (HEK293) cells using a bicistronic vector. Deletion of the last 30 amino acids of the carboxyl terminus of ECaC1 (G701X) decreased the Ca(2+) sensitivity significantly. Another critical sequence for Ca(2+)-dependent inactivation of ECaC1 was found upstream in the carboxyl terminus. Analysis of truncations at amino acid 635, 639, 646, 649 and 653 disclosed a critical sequence involved in Ca(2+)-dependent inactivation at positions 650-653. C653X showed decreased Ca(2+) sensitivity, comparable to G701X, while E649X lacked Ca(2+)-dependent inactivation. Interestingly, the number of green fluorescent cells, which is an index of the number of transfected cells, was significantly smaller for cells transfected with truncations shorter than E649 than for cells transfected with wild-type ECaC. However, the expression level of GFP was restored in the presence of the ECaC blocker ruthenium red, suggesting that these truncations resulted in deleterious Ca(2+) influx. In conclusion, we have identified two domains in the carboxyl terminus of ECaC1 that control Ca(2+)-dependent inactivation.     

Immune activation modulates hematopoiesis through interactions between CD27 and CD70

The differentiation of hematopoietic stem cells into mature blood cell lineages is tightly regulated. Here we report that CD27, which is expressed on stem and early progenitor cells in bone marrow, can be important in this process. Deletion of CD27 increased the myeloid colony-forming potential of stem and early progenitor cells and enhanced B lymphoid reconstitutive capacity in competitive transplantation experiments. Conversely, stimulation of CD27(+) progenitor cells with CD70, the unique ligand for CD27, inhibited colony-forming potential in vitro and lymphocyte outgrowth in vivo. As CD70 is expressed only on activated immune cells, we suggest that CD27 triggering on early progenitor cells provides a negative feedback signal to leukocyte differentiation during immune activation.     

氧分压在体监测仪的研制

作者报道一种稳定性较高的氧分压在体监测，为医学研究、临床诊断提供一种新的可靠的测试方法及设备，具有较大的应用价值。     

恶性疟原虫113肽抗原基因重组的减毒鼠伤寒沙门菌在家兔中免疫应答的研究

我们已经在减毒鼠伤寒沙门菌ＳＬ３２６１以融合蛋白的形式表达了人工合成的恶性疟原虫杂合１１３肽基因ＡＢ（ＧＺ－ＡＢ）。活菌以２×１０９ＣＦＵ经口服免疫新西兰家兔，用ＥＬＩＳＡ测定抗体水平，结果于首次免疫或加强免疫后都可检测到一定水平的特异性抗体。所免疫的家免可以诱发针对恶性疟原虫抗原及ＧＺ－ＡＢ的迟发性超敏反应（ＤＴＨ）。我们的研究表明，含有多个恶性疟原虫抗原表位的人工合成基因可以在减毒鼠伤寒沙门菌中表达，活菌可诱发家兔产生特异的体液免疫及细胞免疫，为恶性疟口服活菌苗的制备打下基础。     

大鼠脊髓损伤后NGF及其受体TrkA在运动神经元及神经胶质细胞表达的变化

为探讨脊髓损伤后运动神经元及神经胶质细胞内神经生长因子(NGF)及其高亲和力受体(TrkA)表达的变化,用改良Allen重击法损伤SCI组动物T12脊髓,按伤后存活时间再将动物分为脊髓损1 d组、2 d组和5 d组。各组动物的脊髓切片经ABC法免疫组织化学染色,用光镜观察TrkA及NGF在脊髓前角运动神经元表达的变化和胶质纤维酸性蛋白(GFAP)及NGF免疫反应阳性胶质细胞的反应性增生程度,并进行图像分析。结果显示:脊髓损伤后前角运动神经元TrkA及NGF的表达随脊髓损伤后动物存活时间的延长逐渐上调;脊髓白质和灰质内尤其是皮质脊髓束内GFAP及NGF阳性胶质细胞明显增生;与此同时,室管膜细胞内亦可见明显的NGF免疫反应产物。上述结果表明,脊髓损伤可刺激脊髓前角运动神经元表达TrkA及NGF,通过自分泌维持受损神经元的存活;损伤部位反应性增生的胶质细胞亦可产生NGF,通过旁分泌作用于脊髓前角运动神经元或皮质脊髓束的轴突末梢,以维持运动神经元的存活及促进皮质脊髓束的再生;适时补充外源性神经营养素或改变损伤局部的微环境将有利于受损脊髓的修复和再生。