Helminthosporoside,a host-specific toxin fromHelminthosporium sacchari: A structure revision and a new partial structure

Summary Reevaluation of the previously proposed structure of helminthosporoside, a host-specific toxin fromHelminthosporium sacchari, reveals a sesquiterpenoid bis-digalactoside. The carbohydrate portion of the toxin was characterized by¹³C-NMR spectroscopy, methylation analyses, FD and FAB mass spectroscopy. The ring size and anomeric configuration of the galactose moieties were determined by utilizing a¹³C-NMR structural analysis method. A new partial structure is proposed.Acknowledgment. We extend special thanks to C.E. Costello, Department of Chemistry, M.I.T., Cambridge, MA, for FD mass spectral analyses, and to C.E. Ballou, Department of Biochemistry, University of California, Berkeley, CA, for FAB mass spectral analyses. We submit sincere appreciation to both V.N. Reihold, Harvard Medical School, Boston, MA, and P. Albersheim, Department of Chemistry, University of Colorado, Boulder, CO, for methylation analyses. We thank J.S. Frye at the Colorado State University Regional NMR-Center, funded by National Science Foundation grant No. DHE 78-18581, Department of Chemistry, Colorado State University, Fort Collins, Co, for high resolution CMR and NMR, and we are grateful to P.W. Jennings, Department of Chemistry, Montana State University, Bozeman, Mt, for total carbon analyses. This work was supported in part by a Herman Frasch Foundation grant to G.A. Strobel, by NSF grant PCM-78-22517, and funds from the Montana Agricultural Experiment Station. B.P. Mundy acknowledges the partial support of NSF (ISP-801149).     

基因工程改造噬菌体应用于细菌感染的研究进展

噬菌体作为细菌病毒,在细菌性感染尤其是多重耐药菌感染的治疗方面具有抗生素无法比拟的优势。目前人工改造噬菌体的理论和技术已趋成熟,研究者通过基因工程技术解决了噬菌体特异性高、半衰期短、释放内毒素等问题,使基因工程改造噬菌体具有了较强的临床应用潜力。本文主要就基因工程改造噬菌体在扩大宿主范围、增强抗生素疗效、延缓免疫清除、避免内毒素释放等方面所具有的优势,及其在剂量确定、细菌耐受、宿主安全性等方面可能会出现的问题进行了阐述。     

Examination of the potential mutagenicity of hair dye constituents using the micronucleus test

Summary 12 compounds which are constitutents of hair dyes or chemically related aromatic amines, aminophenols, their nitroderivatives and aromatic hydroxyderivatives were examined for evidence of mutagenic potential by means of the micronucleus test. None of the compounds tested caused an increase in the incidence of micronucleated erythrocytes after oral dosing.Acknowledgment. These investigations were conducted on behalf and with the assistance of Elida-Gibbs GmbH, Hamburg, Goldwell GmbH, Darmstadt, Thera-Chemie GmbH, Dusseldorf, L'Oreal-Haarkosm, und Parf. GmbH, Karlsruhe, Kadus-Werk K.G., Lenzkirch, Hans Schwarzkopf GmbH, Hamburg, Wella AG, Darmstadt.     

Melatonin,clock genes and mitochondria in sepsis

After the characterization of the central pacemaker in the suprachiasmatic nucleus, the expression of clock genes was identified in several peripheral tissues including the immune system. The hierarchical control from the central clock to peripheral clocks extends to other functions including endocrine, metabolic, immune, and mitochondrial responses. Increasing evidence links the disruption of the clock genes expression with multiple diseases and aging. Chronodisruption is associated with alterations of the immune system, immunosenescence, impairment of energy metabolism, and reduction of pineal and extrapineal melatonin production. Regarding sepsis, a condition coursing with an exaggerated response of innate immunity, experimental and clinical data showed an alteration of circadian rhythms that reflects the loss of the normal oscillation of the clock. Moreover, recent data point to that some mediators of the immune system affects the normal function of the clock. Under specific conditions, this control disappears reactivating the immune response. So, it seems that clock gene disruption favors the innate immune response, which in turn induces the expression of proinflammatory mediators, causing a further alteration of the clock. Here, the clock control of the mitochondrial function turns off, leading to a bioenergetic decay and formation of reactive oxygen species that, in turn, activate the inflammasome. This arm of the innate immunity is responsible for the huge increase of interleukin-1β and entrance into a vicious cycle that could lead to the death of the patient. The broken clock is recovered by melatonin administration, that is accompanied by the normalization of the innate immunity and mitochondrial homeostasis. Thus, this review emphasizes the connection between clock genes, innate immunity and mitochondria in health and sepsis, and the role of melatonin to maintain clock homeostasis.     

Bromocriptine-induced removal of endoplasmic membranes from prolactinoma cells

Summary Adenomatous prolactin cells lose 39% of their cytoplasm volume within 7 days after the beginning of bromocriptine treatment. A simultaneous reduction of the rough-surfaced endoplasmic reticulum and the Golgi apparatus occurs. Their membranes are removed by rapid transport along the secretory pathway to the cell surface and to lysosomal destruction.We thank Prof. E. del Pozo, Sandoz Ltd, Basle, for the generous gift of injectable bromocriptine, Prof. E.R. Weibel, Dept. of Anatomy, University of Bern, for his technical advice, Dr U. Helfenstein, Institute of Biostatistics, University of Zürich, for his help in the statistical evaluation of the results and the EMDO-Foundation, Zürich, for financial support.     

Chemistry and Chemists at the London Institution 1807-1912

The London Institution, established in the City of London in 1807, was devoted, as its full title proclaimed, to the 'advancement of Literature and the Diffusion of Useful Knowledge'. With its extensive lecture programme, splendid reference library, reading rooms, laboratory and other amenities, it provided for its members a scientific and cultural centre, modelled on the highly successful and fashionable Royal Institution in London's West End. Among its scientific activities, chemistry long maintained a leading role, in terms of both the sheer volume and variety of its presentations, and the high standing of its lecturers; they included Faraday, Playfair, Hofmann, Roscoe, Odling, Norman Lockyer, Meldola, and Sir William Ramsay, as well as other visiting lecturers, specially selected for their ability to present their subject in an interesting and attractive fashion to a wider lay public. The laboratory of the Institution, although limited in size and facilities, was the scene of instruction in practical chemistry, and between 1863 and 1884 attained the reputation of a significant centre of chemical research during the successive tenure of the professorship in chemistry by J. A. Wanklyn and H. E. Armstrong. Their publications, appearing under the device 'From the Laboratory of the London Institution', were a frequent feature of the leading chemical periodicals. Thus, within its many-sided activities, the Institution promoted significantly the public appreciation of the function of chemistry, as a contributor both to pure knowledge, and to technical and economic progress. It achieved this in an environment of influential City merchants, manufacturers and financiers and doubtless led to beneficient, if unrecorded, consequences. It was only towards the close of the nineteenth century, when the universities had become increasingly concerned with the systematic study of the discipline, that chemistry lost its direct impact in the London Institution, but continued to maintain a presence within its cultural framework.     

Fred Neufeld and pneumococcal serotypes: foundations for the discovery of the transforming principle

During the first decade of the twentieth century, the German bacteriologist Fred Neufeld, later Director of the Robert Koch-Institute in Berlin, first described the differentiation of pneumococci into serotypes on the basis of type-specific antisera. This finding was essential for subsequent research at the Rockefeller Institute of Medical Research (RIMR) in New York, and elsewhere, aiming for the conquest of human pneumococcal pneumonia, including antiserum therapy, the discovery that the type-specific antigens were carbohydrates, and the development of effective multivalent pneumococcal polysaccharide vaccines. Moreover, on the basis of pneumococcal serotypes Fred Griffith, in 1928 in London, discovered pneumococcal transformation, and Oswald T. Avery and coworkers, in 1944 at RIMR, identified DNA as the transforming substance. This sequence of events, leading to today’s knowledge that genes consist of DNA, was initiated by a farsighted move of Simon Flexner, first Director of the RIMR, who asked Neufeld to send his pneumococcal typing strains, thus setting the stage for pneumococcal research at RIMR. Here, we describe Fred Neufeld’s contributions in this development, which have remained largely unknown.     

药用植物羌活现状及其民族植物学调查

羌活为重要的传统中药和藏药常用药材，大量的汉藏药方和成药均作为重要的配伍药材加以使用。羌活传统产区主要是藏族、羌族和其它少数民族的聚居的高寒山区，经济较为落后，交通不便。由于难以驯化栽培，药材来源主要依赖野生资源采挖，但由于受到种子发育不完全、后熟期长等本身繁殖特性的限制，羌活繁殖和种群恢复主要是通过无性繁殖实现，野生资源恢复受到严重制约。道地产区的调查发现，羌活野生生境正受到前所未有的破坏，包括生境丧失、破碎化、土壤退化、土地利用模式改变和环境变化等；调查还发现近年来羌活药材价格与采挖量之间的关系，以及当地民族植物学方面的状况。羌活野生资源的破坏受到利益驱使、致使采挖时间和方式等利用模式发生改变，极不利于羌活野生资源的保存和种群恢复，若不规范羌活野生资源的利用和引种驯化，进行人工栽培，羌活野生资源不但难以实现可持续利用，而且还将遭到毁灭性破坏，并有灭绝的危险。本文最后提出了药用羌活属植物的保护性开发和可持续利用可能途径。     

Acetylsalicylic acid-induced morphological changes in the ductus arteriosus of the chick embryo

Summary The effect of acetylsalicyclic acid upon the ducti arteriosi of the embryonic chick was studied. A spectrum of gross malformations and histological findings associated with premature closure of the right ductus arteriosus is presented.This study was supported by grant No. HL18050, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland. The authors wish to extend their appreciation to John M. Opitz, University of Wisconsin Department of Genetics, for his generous support. This report was presented in part at the Fiftieth Scientific Sessions, American Heart Association Meetings, Miami, Florida, November 1977.     

Lipid-lowering drugs

Although a change in life-style is often the method of first choice for lipid lowering, lipid-lowering drugs, in general, help to control elevated levels of different forms of lipids in patients with hyperlipidemia. While one group of drugs, statins, lowers cholesterol, the other group, fibrates, is known to take care of fatty acids and triglycerides. In addition, other drugs, such as ezetimibe, colesevelam, torcetrapib, avasimibe, implitapide, and niacin are also being considered to manage hyperlipidemia. As lipids are very critical for cardiovascular diseases, these drugs reduce fatal and nonfatal cardiovascular abnormalities in the general population. However, a number of recent studies indicate that apart from their lipidlowering activities, statins and fibrates exhibit multiple functions to modulate intracellular signaling pathways, inhibit inflammation, suppress the production of reactive oxygen species, and modulate T cell activity. Therefore, nowadays, these drugs are being considered as possible therapeutics for several forms of human disorders including cancer, autoimmunity, inflammation, and neurodegeneration. Here I discuss these applications in the light of newly discovered modes of action of these drugs. Received 5 September 2005; received after revision 29 December 2005; accepted 26 January 2006     

解聚复肾宁对糖尿病大鼠肾脏HGF表达的影响

目的观察解聚复肾宁（JJFSN）对糖尿病大鼠肾HGF表达的影响及肾保护作用。方法SD大鼠腹腔注射链尿佐菌素法建立糖尿病模型,随机分为正常对照组、模型组、解聚复肾宁治疗组、依那普利治疗组、JJFSN＋依那普利治疗组。12周后,检测各组空腹血糖（FBG）、尿素（BU）、24h尿β2微球蛋白（β2-MG）、肌酐清除率（Ccr）;免疫组化法检测肾组织HGF表达,放射免疫法测定大鼠血清胰岛素（Ins）含量,透射电镜观察肾脏超微结构。结果与模型组比较,各治疗组大鼠FBG、BU、β2-MG明显降低,Ccr明显升高,血清Ins含量增加,肾组织HGF表达明显上调,肾组织病理变化减轻,其中以J＋Y组改善最显著（P〈0．05）。结论JJFSN对DM大鼠肾脏形态争功能有明显保护作用,其机制可能与其上调肾脏HGF表达、保护胰岛β细胞、延缓肾脏纤维化进程有关。     

The presence of free D-serine, D-alanine and D-proline in human plasma.

Twelve neutral free amino acids, i.e. serine, threonine, glutamine, asparagine, alanine, proline, methionine, tyrosine, valine, leucine, isoleucine and phenylalanine, were surveyed for the presence of D-enantiomers in plasma samples from patients with renal diseases and from normal subjects. D-serine, D-alanine and D-proline were found in the patient's plasma. The highest concentrations (D/L ratio) of D-serine, D-alanine and D-proline were 0.2362, 0.2087 and 0.0986, respectively. The sum of the contents of the three D-amino acid was shown to be present in the plasma proteins.     

Periostin in the pathogenesis of skin diseases

Skin is an organ that is susceptible to damage by external injury, chronic inflammation, and autoimmunity. Tissue damage causes alterations in both the configuration and type of cells in lesional skin. This phenomenon, called tissue remodeling, is a universal biological response elicited by programmed cell death, inflammation, immune disorders, and tumorigenic, tumor proliferative, and cytoreductive activity. In this process, changes in the components of the extracellular matrix are required to provide an environment that facilitates tissue remodeling. Among these extracellular matrix components, periostin, a glycoprotein that is predominantly secreted from dermal fibroblasts, has attracted attention. Periostin localizes in the papillary dermis of normal skin, and is aberrantly expressed in the dermis of lesional skin in atopic dermatitis, scar, systemic/limited scleroderma, melanoma, cutaneous T cell lymphoma, and skin damage caused by allergic/autoimmune responses. Periostin induces processes that result in the development of dermal fibrosis, and activate or protract the immune response. The aim of this review was to summarize recent knowledge of the role of periostin in the pathogenesis of dermatoses, and to explore whether periostin is a potential therapeutic target for skin diseases.     

Timing of action of sperm proteases in ascidian fertilization

Summary The timing of action of three sperm proteases, acrosin, spermosin, and a chymotrypsin-like enzyme, in the fertilization of the ascidian,Halocynthia roretzi, was examined by adding specific protease inhibitors at various times after insemination. The results indicate that the last two enzymes both function at the early stage of the process of sperm penetration through the egg investment, while acrosin functions at the late stage.Acknowledgments. We are indebted to Dr M. Hoshi of Tokyo Institute of Technology for his helpful discussion, and to Dr T. Someno of Nippon Kayaku Kogyo Co. for his generous gifts of Z-Val-Pro-Arg-H and leupeptin. This work was supported by Grants-in-Aid from the Ministry of Education, Science and Culture of Japan, and from Naito Research Foundation.     

Determination of trace elements in peripheral lymphocytes from tumor-bearing rats.

Neutron activation analysis of peripheral lymphocytes from healthy and Walker 256 carcinosarcoma-bearing rats resulted in the quantitative determination of Co, Cu, K, Mn, Rb, Se and Zn, and a qualitative determination of Au and Sb. From corresponding plasma samples, Co, Zn, Rb, Se and Cs were analyzed. Differences in trace element concentrations could only be detected in plasma of tumor-bearing animals which showed a decreased Zn and Co content of 50% and 30%, respectively, and a rise of Rb when compared to plasma of control animals.     

Leibniz on the requisites of an exact arithmetical quadrature

In this paper we will try to explain how Leibniz justified the idea of an exact arithmetical quadrature. We will do this by comparing Leibniz's exposition with that of John Wallis. In short, we will show that the idea of exactitude in matters of quadratures relies on two fundamental requisites that, according to Leibniz, the infinite series have, namely, that of regularity and that of completeness. In the first part of this paper, we will go deeper into three main features of Leibniz's method, that is: it is an infinitesimal method, it looks for an arithmetical quadrature and it proposes a result that is not approximate, but exact. After that, we will deal with the requisite of the regularity of the series, pointing out that, unlike the inductive method proposed by Wallis, Leibniz propounded some sort of intellectual recognition of what is invariant in the series. Finally, we will consider the requisite of completeness of the series. We will see that, although both Wallis and Leibniz introduced the supposition of completeness, the German thinker went beyond the English mathematician, since he recognized that it is not necessary to look for a number for the quadrature of the circle, given that we have a series that is equal to the area of that curvilinear figure.