人体肠道病毒组学研究进展

人体微生物组计划开展近10年来,大量的研究显示人体微生物通过各种方式深刻地影响着人体健康。人体肠道内丰富多样的病毒构成了肠道病毒组,是人体微生物组的重要组成部分,和人体健康密切相关。本文综述了近些年国际上人体肠道病毒组研究的最新进展,分别从人体肠道病毒组的组成特征、肠道病毒组-细菌组-人体间的相互作用及其对人体健康的影响、病毒组研究的技术策略及挑战等方面进行了论述,探讨了肠道病毒组在人体疾病预防和治疗领域应用的可行性。     

Adaptive sequence divergence forged new neurodevelopmental enhancers in humans

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Efficient production of human tumour necrosis factor in Escherichia coli

Human tumour necrosis factor (TNF) cDNA was isolated from a cDNA library prepared using TNF mRNA from human alveolar macrophages. Using the cDNA, various expression plasmids were constructed and their TNF producibility was examined in Escherichia coli. The best transformants produced a TNF polypeptide in a yield of about 20% of cellular proteins. The purified TNF polypeptide was lacking a methionine residue at the N-terminus, and possessed the expected physical and chemical properties and the biological activities characteristic of TNF.     

古人类对赭石的利用行为在其演化中的意义

长期以来赭石利用行为被视为人类行为现代性的标志之一,受到国内外考古学界的普遍关注。本文回溯和梳理了全球背景下赭石利用的起源、发展及其与人类演化史的关系。在现代人广泛分布于全球之后,赭石利用行为更加丰富和多样化地出现在各地,然而现有考古证据表明该行为并不是解剖学意义上的现代人突变性的发明。赭石利用不能被单纯地定义为现代人行为,而应是有着长久演化积累的现代性行为之一。在长期传播与演化过程中,赭石的功能从意识形态、艺术表达等逐渐扩展到作为矿物成分被用于实际生产生活。赭石的利用历史可追溯到中更新世中期,但其广泛分布仍与晚更新世以来现代人的广泛扩散直接相关,对于理解现代人的意识形态、社会组织方式以及艺术表达、精神文化发展都具有重要的意义。国内目前所发表的相关考古学证据相对较少,以下马碑遗址为代表的材料,也恰处于现代人在全球广泛扩散的窗口期,并伴有进步的细小石器镶嵌使用的证据,成为认识东亚现代人行为的关键性考古证据。     

Ethical Issues in the Use of Data from Testing of Human Subjects to Support Risk Assessment

The public understands and supports the ethical use of human subjects in medical research, recognizing the unique role for this type of study in the development of new drugs and therapeutic strategies for treatment of disease. The use of data from human subjects can also be of value in understanding the circumstances under which individuals exposed to chemicals in the food supply, in the workplace, or in the environment might experience toxicity, i.e., in support of risk assessment. However, questions have been raised as to whether this latter type of research is ethical, or can be performed in an ethical manner. Under what circumstances is it acceptable to intentionally expose human subjects to potentially toxic agents? This is an extremely important issue for the risk assessment community to address, because it affects in a fundamental way the types of information that will be available to conduct human health risk assessments. Four papers in this issue offer viewpoints on the value of human data, the circumstances under which human subjects might be exposed to toxic chemicals for research purposes, the ethical problems associated with this research, and the role of human vs. animal data in the development of toxicity values for human health risk assessment     

Activation of human neutrophils with Helicobacter pylori and the role of Toll-like receptors 2 and 4 in the response

The innate immune response to Helicobacter pylori infection is beginning to be understood and recent works support a role for Toll-like receptors (TLRs). Our aim was to study the response of human neutrophils to H. pylori and to elucidate the role of TLR2 and TLR4. Neutrophils from healthy H. pylori-negative volunteers were cocultured with H. pylori 26695 strain. The release of IL-8, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-10 was measured. The role of TLR2 and TLR4 was investigated with blocking assays using monoclonal antibodies against TLRs. Neutrophils produced a significant increase of IL-8, IL-1beta and TNF-alpha after 3, 6 and 24 h of H. pylori challenge, respectively, whereas IL-10 increased after 24 h. Helicobacter pylori challenge increased TLR2 and TLR4 expression; and antibodies against TLR2 and TLR4 diminished significantly the H. pylori-induced production of IL-8 and IL-10. In human neutrophils, H. pylori induces an early inflammatory response, partially mediated via TLR2 and TLR4 activation.     

Neurotensin increases net fluid secretion and transit rate in the small intestine of man

In a double-blind study with six patients, who previously had undergone proctocolectomy for ulcerative colitis, the ileostomy discharge significantly increased from 110 to 295 ml X 4 h-1 during infusion of neurotensin, 3 pmol X kg-1 X min-1 for 4 h. Transit defined as the passage of a perorally ingested unabsorbable marker (polyethylene glycol, PEG 4000) was significantly increased during the last hour of neurotensin infusion. The dose of neurotensin used in this study has previously been shown to result in plasma levels of neurotensin-like immunoreactivity within the range obtained after a fatty meal. Thus, the present data indicate that neurotensin in man may exert a physiological function by increasing net fluid secretion in the small intestine as well as increasing the intestinal transit rate.     

人血清白蛋白纯化技术研究进展

本文综述了国内外关于血浆人血清白蛋白（pHSA）和基因重组人血清白蛋白（rHSA）分离纯化的进展和发展趋势。以冷乙醇沉淀为主的pHSA分离方法仍是目前多数工业采用的工艺,但近年来发展的离子交换色谱、凝胶过滤色谱、亲和色谱等多种色谱分离技术具有自动化程度高、生产周期短、更符合GMP等特点,正在逐步取代传统的冷乙醇沉淀法。当前用基因工程技术表达的人血清白蛋白对分离纯化提出了新的挑战。为获得高纯度、安全、稳定的产品,各种色谱分离技术得到更多的应用,其中扩张床离子交换色谱可以省去离心、过滤等传统固液分离操作。尽管rHSA的纯化技术已有一定的发展,但纯化过程仍需进一步优化以提高产品纯度及收率。     

The Practical Mode—A Distinct Mode of Performance in Biology

Linnaeus' timely work was a major contribution to botany and is of interest to students of botany at all levels. This is a brief biographical outline with a version of his Flora's Clock which some might like to try.     

Application of PIXE analysis to the study of the regional distribution of trace elements in normal human brain

A particle-induced X-ray emission (PIXE) analysis method is presented, which allows measurement of eight elements (i.e., K, Ca, Mn, Fe, Cu, Zn, Se, and Rb) in human brain samples of only a few mg dry weight. The precision and accuracy of the method were investigated by analyzing animal brain matter with both PIXE and instrumental neutron activation analysis (INAA). The method was applied to measure the 8 elements in 46 different regions of 3 human brains. The sections analyzed originated from either the left or the right cerebral hemisphere, brain stem, and cerebellum. For one of the brains, sections were also analyzed from 26 corresponding regions of both hemispheres. For all elements, similar concentrations were found in the corresponding areas of the left and right sides of the brain. The concentrations (in μg/g dry weight) of the elements K, Fe, Cu, Zn, Se, and Rb were consistently higher in cortical structures than in white matter. Deep nuclei and brain stem, which have a mixed composition, showed intermediate values for K, Zn, Se, and Rb. A hierarchical cluster analysis indicated that the various brain regions clustered into two large groups, one comprising gray and mixed matter regions and the other, white and mixed matter brain areas.     

Characterization of an in vitro system of human renal papillary collecting duct cells

Summary We have developed an in vitro model of human papillary collecting duct cells isolated from cadaver kidneys using methods similar to those we previously reported for the isolation of human proximal tubule cells. To date we have isolated papillary collecting duct cells from 100 normal human kidneys. Papillae were dissected and digested in Cellgro containing 400 U/ml collagenase. Cells were plated on fibronectin-coated culture flasks at a density of 10⁴ live cells/ml in Cellgro supplemented with insulin and 10% fetal bovine serum. Confluent monolayers, which were able to withstand 600 mOsm for 8 h, were obtained within 10 to 15 d. Cells of primary isolates and first passages exhibited epithelial cell ultrastructure including cell junctions, microvilli, and cilia. A dark-brown reaction product was observed in these cells when stained by the immunoperoxidase method with peroxidase-labeled peanut lectin (Arachis hypogaea), which binds specifically to human distal tubule and collecting duct cells. These cells were negative for Factor-VIII (a marker for endothelial cells) and γ-glutamyltransferase (a marker for proximal tubule cells). High activities of the glycolytic enzyme pyruvate kinase and arginine vasopressin-stimulated cAMP production in these cells are consistent with a distal nephron origin. The results indicate that human collecting duct cells can be isolated and cultured to provide an in vitro system to probe pathogenetic mechanisms of potential nephrotoxins. Part of this work was presented at a Symposium of the Center for Alternatives to Animal Testing, April 4–5, 1989, Johns Hopkins Medical Institutions, Baltimore, MD 21205. This work was supported in part by grants R01-AI24179, PO1-A804393 for the Public Health Service, U.S. Department of Health and Human Services, and by a grant from the National Kidney Foundation, Baltimore, MD affiliate.     

The Concept of Human Dignity in the Ethics of Genetic Research

Despite criticism that dignity is a vague and slippery concept, a number of international guidelines on bioethics have cautioned against research that is contrary to human dignity, with reference specifically to genetic technology. What is the connection between genetic research and human dignity? In this article, I investigate the concept of human dignity in its various historical forms, and examine its status as a moral concept. Unlike Kant's ideal concept of human dignity, the empirical or relational concept takes human dignity as something that is affected by one's circumstances and what others do. I argue that the dignity objection to some forms of genetic research rests on a view of human nature that gives humans a special status in nature – one that is threatened by the potential of genetic research to reduce individuals to their genetic endowment. I distinguish two main philosophical accounts of human nature. One of these, the Aristotelian view, is compatible with the use of genetic technology to help humans realize their inherent potential to a fuller extent.     

人胚胸腺组织移植对晚期癌症患者外周血T细胞亚群的微生态影响

本文比较了晚期癌症患者和进行人胚胸腺移植的晚期癌症惠者与正常人T细胞的免疫微生态学关系。结果表明:晚期癌症患者的免疫微生态平衡失调,总T细胞和辅助性T细胞(T_H)均明显减少,抑制性T细胞(T_H)显著增多,T_H/T_S细胞比值显著降低。进行人胚胸腺组织移植后。患者的免疫微生态环境有所改善,T_H细胞有显著增高,TS有明显下降,T_H/T_S细胞比值显著升高。本研究证明晚期癌症患者免疫微生态环境发生紊乱,免疫系统受抑制,由于肿瘤的转移,手术切除原发癌灶后,免疫抑制仍未解除。进行人胚胸腺组织移值则可使其免疫微生态趋于平衡,免疫功能增强,利于延长患者寿命。     

Development of Antibody to Human GM3 Synthase and Immunodetection of the Enzyme in Human Tissues

Polyclonal antibody was raised to a cloned fragment of human GM3 synthase. Affinity purified R27C1 antibody to the tagged recombinant protein inhibited GM3 synthase activity in human liver and HL-60 cells in a dose-dependent manner. However, the R27C1 antibody did not affect liver sialyltransferase activity towards asialofetuin. We are the first to measure GM3 synthase activity in human liver (194 +/- 60 pmol NeuAc/h per mg protein), which was about 10-fold lower than in phorbol myristate acetate-stimulated HL-60 cells (1353 +/- 573 pmol NeuAc/h per mg protein). On immunoblotting the R27C1 antibody recognized a common protein band in a number of human tissues (liver, brain, atherosclerotic aortic intima, HL-60 cells) with molecular mass of about 60 kD, which is similar to that of the purified GM3 synthase from rat liver. In human liver and aortic intima, the 60-kD band was almost a single band, which makes possible the use of the R27C1 antibody for immunohistochemical studies in these tissues.     

Ultrastructure of human spleen in transmission and scanning electron microscope

Despite new information concerning functional morphology of spleen, there are still some inaccuracies mostly regarding the spleen blood circulation. Billroth’s (splenic) cords are formed from three-dimensional network of fibroblastic reticular cells located among branched sinuses. Results from our study using scanning electron microscopy confirm an intimate contact between adjacent reticular cells and erythrocytes. Arterial terminals can be observed in the Billroth’s cords. The wall of sinuses reminds a sieve and it is lined with a special type of endothelium. In electron microscope, endothelial cells look like rods oriented parallel to the longitudinal axis of sinuses. Based on our observations fibroblastic reticular cells change to fixed phagocytes under no circumstances, hence they do not participate in phagocytosis. They may have a recognition function for cells circulating around them. According to our opinion, the open and the closed blood circulation are present in the human spleen simultaneously. Blood flowing in the closed circulation can help “absorption” of extra-vascular liquid and the blood elements into the vascular lumen. Due to sporadic occurrence of smooth muscle cells in the capsule and trabeculae, we assume that human spleen is not a blood reservoir, unlike the spleen in some other animals.     

Amniogenesis occurs in two independent waves in primates

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