243例健康人血红细胞悬浮液射频介电特性的研究

本文应用同轴传输线反射法建立的细胞悬浮液介电测量系统，测量了２４３例健康人（男１２０，女１２３名）血红细胞悬浮液在１～５００ＭＨｚ频率范围的介电常数和电导率。结果表明不同性别和不同血型之间的红细胞悬浮液的介电参数无显著差异。将１９～８０岁之间的受试者按１０岁年龄间隔分成六个组，探讨年龄差别对介电参数的影响；发现５０岁左右是人红细胞介电参数有显著差异的临界年龄，４９岁后三个高年龄组的介电参数显著地低于４９岁前的三个低年龄组的数值（Ｐ＜０．０５）。本文的结果证明年龄对人血红细胞的介电参数有明确的影响。     

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.     

Mineralization behaviour of collagen type I immobilized on different substrates

Collagen type I as a robust fibre protein and main component of the extracellular matrix of most tissues is increasingly utilized for surface engineering of biomaterials using different immobilization methods. In the present work we studied the mineralization behaviour of fibrillar collagen type I in simulated body fluid as a measure for conformational changes caused by adsorptive immobilization or immobilization by partial incorporation into the anodic oxide layer on c.p.-titanium using microscopic and vibration spectroscopic methods. Adsorptive immobilization on highly oriented pyrolytic graphite (HOPG) and c.p.-titanium without collagen were used as references. In the initial phase (1-24 h) the kinetics of formation and the morphology of calcium phosphate phases (CPP) are strongly influenced both by the substrate and the immobilization method. Compared to HOPG both types of immobilization on titanium increasingly inhibit the formation of CPP. For longer times (30 d) these initial differences disappear-mineralization product on titanium, irrespective of the presence of collagen, is a mixture of amorphous calcium phosphate and octacalcium phosphate. Contrary to this the mineralization of HOPG substrates results in hydroxy apatite. This is discussed with respect to the conditions during the immobilization as well as the resulting interactions between substrate and immobilized collagen. It is shown that the mineralization process exhibits a high sensitivity with respect to conformational changes caused by these interactions. Possible cell biological relevance of these conformational changes is discussed.     

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.     

Na/P(i) cotransporter ( Npt2) gene disruption increases duodenal calcium absorption and expression of epithelial calcium channels 1 and 2

Mice homozygous for the disrupted type-II Na/P(i) cotransporter gene ( Npt2(-/-)) exhibit hypophosphataemia, increased serum concentration of 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) and calcium (Ca) and elevated urinary Ca excretion. To determine whether the hypercalcaemia and hypercalciuria are secondary to 1,25-(OH)(2)D-stimulated intestinal Ca absorption, we examined the effect of Npt2 gene disruption on serum Ca and urinary Ca excretion after an overnight fast, and on duodenal Ca absorption. We also compared the duodenal expression of the epithelial Ca channels, ECaC1 and ECaC2, and calbindinD(9K) mRNAs, relative to that of beta-actin mRNA, in Npt2(+/+) and Npt2(-/-) mice. Both serum Ca and urine Ca/creatinine were significantly decreased in Npt2(-/-) mice after an overnight fast and were no longer different from that in wild-type mice. Absorption of (45)Ca from isolated duodenal segments in vivo and (45)Ca appearing in the plasma were significantly increased in Npt2(-/-) compared with Npt2(+/+) mice. In addition, the duodenal abundance of ECaC1, ECaC2 and calbindinD(9K) mRNAs was significantly elevated in mutant mice relative to that in wild-type mice. In contrast, both duodenal Ca absorption and ECaC1 and ECaC2 mRNA abundance were lower in mice with X-linked hypophosphataemia ( Hyp) than in normal littermates. In summary, we provide evidence for increased duodenal Ca absorption in Npt2(-/-) mice and suggest a role for ECaC1, ECaC2 and calbindinD(9K) in mediating this response.     

Clinical and genetic characteristics of Stargardt disease in a large Western China cohort: Report 1

Stargardt disease 1 (STGD1) is the most prevalent retinal dystrophy caused by pathogenic biallelic ABCA4 variants. Forty‐two unrelated patients mostly originating from Western China were recruited. Comprehensive ophthalmological examinations, including visual acuity measurements (subjective function), fundus autofluorescence (retinal imaging), and full‐field electroretinography (objective function), were performed. Next‐generation sequencing (target/whole exome) and direct sequencing were conducted. Genotype grouping was performed based on the presence of deleterious variants. The median age of onset/age was 10.0 (5–52)/29.5 (12–72) years, and the median visual acuity in the right/left eye was 1.30 (0.15–2.28)/1.30 (0.15–2.28) in the logarithm of the minimum angle of resolution unit. Ten patients (10/38, 27.0%) showed confined macular dysfunction, and 27 (27/37, 73.7%) had generalized retinal dysfunction. Fifty‐eight pathogenic/likely pathogenic ABCA4 variants, including 14 novel variants, were identified. Eight patients (8/35, 22.8%) harbored multiple deleterious variants, and 17 (17/35, 48.6%) had a single deleterious variant. Significant associations were revealed between subjective functional, retinal imaging, and objective functional groups, identifying a significant genotype–phenotype association. This study illustrates a large phenotypic/genotypic spectrum in a large well‐characterized STGD1 cohort. A distinct genetic background of the Chinese population from the Caucasian population was identified; meanwhile, a genotype–phenotype association was similarly represented.     

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.     

实验性肾炎中肾皮质内血小板活化因子的水平和可能来源

用大鼠复制加速型抗肾小球基底膜肾炎模型，分为４组：肾毒血清对照组，肾毒血清＋眼镜蛇毒因子组，肾毒血清＋羊抗大鼠血小板血清组，肾毒血清＋全身γ线辐射组。各组大鼠在注射兔抗大鼠ＧＢＭ血清后２４ｈ末处死，结果肾毒血清对照组大鼠肾皮质内ＰＡＦ含量显著升高，而耗尽被 体的肾毒血清＋ＣＶＦ组、耗尽血小板的肾毒血清＋ＡＰＳ组和耗尽血白细胞的肾毒血清＋ＴγＩ组大鼠肾皮质内ＰＡＦ含量低于肾毒血清对照组，正常大鼠肾皮