Protective and immunostimulating activity of a low dose of cyclophosphamide in the experimental infection of mice with foot-and-mouth disease virus

Summary Administration to mice of a low, non-immunosuppressive dose of cyclophosphamide 4 days before infection with foot-and-mouth disease virus decreases viral replication, enhances the immune response against the virus and prevents panceatic damage.     

Protective effect of lidocaine in the experimental foot-and-mouth disease pancreatitis

Experimental infection of mice with foot-and-mouth disease virus (FMDV) induces a necrotizing pancreatitis of the exocrinar portion of the organ. The lesions are characterized by vascular congestion, edema and interstitial polymorphonuclear leukocyte (PMN) infiltrates. When infected mice were treated with different amounts of lidocaine (a local anesthetic, chemically defined as a tertiary amide compound), reduction in intensity of the pancreatic necrosis and in the number of PMN were observed. Even though lidocaine could interfere with FMDV post-replicative cytolytic mechanisms, it appears that protection against pancreatic necrosis is by attenuation of PMN presentation in the infected tissue.     

Protective and immunostimulating activity of a low dose of cyclophosphamide in the experimental infection of mice with foot-and-mouth disease virus

Administration to mice of a low, non-immunosuppressive dose of cyclophosphamide 4 days before infection with foot-and-mouth disease virus decreases viral replication, enhances the immune response against the virus and prevents pancreatic damage.     

Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant

The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces the need for a new generation of immunostimulatory adjuvants. Because adverse effects are a paramount concern in prophylactic immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned about this compound’s mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak version of lipopolysaccharide. Instead, monophosphoryl lipid A’s structure seems to have fortuitously retained several functions needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects. Received 25 April 2008; received after revision 05 June 2008; accepted 10 June 2008     

Decision-making at the surface of the intact or barrier disrupted skin: potential applications for vaccination or therapy

The skin is a highly accessible organ and constitutes an active immunological site. Both these properties make this surface an attractive route for what promises to be a cost-effective, simple, practical and needle-free delivery of vaccines and immunomodulators. Less obvious is the fact that the state of the skin barrier can influence quantitative and qualitative aspects of antigen-specific immune responses. The everyday decision-making at the skin epithelium concerns the choice between the induction of an immune response and the establishment of a state of non-responsiveness (tolerance). This decision is influenced by various factors such as the dose, the route (intact vs barrier-disrupted skin), the cytokine microenvironment and the nature of the antigenic stimulus. By increasing our understanding of how immune responses are regulated in the epidermis we can envisage the development of immunisation protocols aimed at eliciting a protective immune response or inducing tolerance, with direct applications to preventive or therapeutic vaccination, respectively.Received 29 November 2004; received after revision 2 February 2005; accepted 22 February 2005     

The supposed use of the lateral line as an organ of hearing in fish

Zusammenfassung Die Untersuchung tierischer Sinnesorgane mit elektrophysiologischen Methoden kann die funktionellen Eigenschaften des Rezeptors als solchen klarlegen, sie berechtigt aber nicht zu Schlussfolgerungen über die funktionelle Bedeutung des betreffenden Sinnesorgans im Leben des Tieres. Zu solchen Schlussfolgerungen sind Verhaltensversuche erforderlich. Die Nichtbeachtung dieses unterschiedlichen Charakters der nach beiden Methoden erhaltenen Resultate führt zu scheinbaren Widersprüchen und zu unberechtigter Kritik, wovon einige rezente Beispiele angeführt werden.     

A farnesyl arabinoside as an enhancer of glucose transport in rat adipocytes from a soft coral,Sinularia sp.

Separation of a lipophilic extract of a soft coral,Sinularia sp., assayed by enhancement of glucose transport in rat adipocytes, gave farnesyl 4-O--D-arabinopyranosyl--D-arabinopyranoside-2,2,3-triacetate (1a) whose structure was determined by spectroscopy. Enhancers of glucose transport may be useful for the prevention and treatment of diabetic disorders.     

Alexander disease: putative mechanisms of an astrocytic encephalopathy

Alexander disease (AXD) is the first primary astrocytic disorder. This encephalopathy is caused by dominant mutations in the glial fibrillary acidic protein (GFAP) gene, encoding the main intermediate filament of astrocyte. Pathologically, this neurodegenerative disease is characterised by dystrophic astrocytes containing intermediate filament aggregates associated with myelin abnormalities.More than 20 GFAP mutations have been reported. Many of them cluster in highly conserved regions between several intermediate filaments. Contrary to other intermediate filament-related diseases, AXD seems to be the consequence of a toxic gain of function induced by aggregates. This is supported by the phenotype of mice overexpressing human GFAP. Nevertheless, GFAP null mice display myelin abnormalities and blood-brain barrier dysfunction that are present in AXD.Given the pivotal role of astrocytes in brain physiology, there are many possibilities for astrocytes to dysfunction and to impair the functions of other cells. Physiopathological hypotheses are discussed in the frame of AXD.Received 11 April 2003; received after revision 22 July 2003; accepted 31 July 2003Both authors contributed equally to this work.     

疟疾子孢子疫苗的研究进展

本文系统地回顾了疟疾疫苗的发展史,将疫苗研究的发展分为与生物技术的发展密切相关的三个时期;重点阐述了疟疾子孢子疫苗在不同时期的研究进展,并分析了疟疾疫苗研究的现状和面临的困难。     

The causes of Charcot-Marie-Tooth disease

Charcot-Marie-Tooth (CMT) disease serves as the summary term for the most frequent forms of inherited peripheral neuropathies that affect motor and sensory nerves. In the last 12 years, 14 genes have been identified that cause different CMT subforms. The genes found initially are predominantly responsible for demyelinating and dysmyelinating neuropathies. Genes affected in axonal and rare forms of CMT have only recently been identified. In this review, we will focus on the currently known genes that are associated with CMT syndromes with regards to their genetics and function.Received 5 April 2003; received after revision 20 May 2003; accepted 23 May 2003     

The value-ladenness of transparency in science: Lessons from Lyme disease

Both philosophers and scientists have recently promoted transparency as an important element of responsible scientific practice. Philosophers have placed particular emphasis on the ways that transparency can assist with efforts to manage value judgments in science responsibly. This paper examines a potential challenge to this approach, namely, that efforts to promote transparency can themselves be value-laden. This is particularly problematic when transparency incorporates second-order value judgments that are underwritten by the same values at stake in the desire for transparency about the first-order value judgments involved in scientific research. The paper uses a case study involving research on Lyme disease to illustrate this worry, but it responds by elucidating a range of scenarios in which transparency can still play an effective role in managing value judgments responsibly.     

The use of complexes of lymphocyte antigens with antibody as immunogens for the preparation of antilymphocytic sera

Résumé Des complexes antigène-anticorps préparées par réaction du sérum antilymphocytaire (ALS) avec des lymphocytes ou avec des broyats lymphocytaires furent injectées aux lapins. Les ALS obtenu ainsi des lapins furent immunodépresseurs. Cette technique peut être utilisée pour obtenir des ALS plus specifique et moins toxique.

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Acknowlegments. We are indebted to our colleagues in the ALS Project Group of these Laboratories for much help and advice.     

The use of microtiter plates for the simple and sensitive determination of insulin by an ELISA method

Summary A method of insulin determination using a commercially available ELISA kit was modified for use in microtiter plates. The adapted assay, based on the binding of procine anti-guinea pig insulin antibodies to microtiter plates and insulin-peroxidase conjugate as displacer, is sensitive between 0.5 and 30 ng/ml. Since it uses only 10–40 l of sample material it enables the determination of 5–100 pg of insulin. The rapid (5–6 h), automatable, reproducible and reliable assay makes it possible to determine many samples in a short time.     

The use of microtiter plates for the simple and sensitive determination of insulin by an ELISA method

A method of insulin determination using a commercially available ELISA kit was modified for use in microtiter plates. The adapted assay, based on the binding of porcine anti-guinea pig insulin antibodies to microtiter plates and insulin-peroxidase conjugate as displacer, is sensitive between 0.5 and 30 ng/ml. Since it uses only 10-40 microliter of sample material it enables the determination of 5-100 pg of insulin. The rapid (5-6 h), automatable, reproducible and reliable assay makes it possible to determine many samples in a short time.     

Bacterial localization: The use of an autographic method for the study of infectious processes in mice

Riassunto Il metodo autografico è stato impiegato per la valutazione della distribuzione dei germi. Sezioni sagittali complete di topi precedentemente infettati sono state incubate e i germi vivi sono stati rivelati mediante colorazione vitale con trifeniltetrazolio. Le risultanti mappe dettagliate della distribuzione batterica permettono di penetrare il meccanismo dei processi difensivi dell'ospite e le proprietà invasive del germe.     

The activity of erythrocyte glucose-6-phosphate dehydrogenase as an indicator of the rate of erythropoiesis

Zusammenfassung Bei 29 Patienten mit verschiedenen hämatologischen Affektionen wurde eine positive Korrelation zwischen Glucose-6-phosphatdehydrogenase-Aktivität der Erythrozyten und dem Erythrozyten-Eisenumsatz gefunden.